Five different drying profiles, including a single triangular shape temperature pattern, two constant and two time-varied schemes were examined, aiming to minimize the drying duration and maintain the product quality. The profile that temperature was gradually increased from 35 ◦C to 60 ◦C within 8 h, was found to be the most appropriate in terms of quality retention  and drying duration. A different study by Xanthopoulos et al., evaluated two stepwise drying schemes, following a step-up and a step-down temperature profile on apricot halves. The constant temperature drying at 55 ◦C had almost the same drying duration with the step-up profile using three temperature stages of 40–55-70 ◦C. The step-up profile presented improved antioxidant activity under the treatment with ascorbic acid and almost a constant drying rate that was initially lower than the constant temperature drying. However, the drying was stopped at MR = 0.35 and no conclusions can be drawn for the final moisture content of apricot halves. Non-stationary temperature schemes of convective drying with an increase of air drying temperature, is reported to have a shorter or almost equal drying duration compared with the low constant drying temperatures and improved effects on quality, compared with the high constant temperature drying. However, given each product’s morphological properties, the appropriate rate of temperature increase and the selection of lower/upper temperature limits can affect differently the quality and the drying time. Thus, one gap that needs to be addressed is how the moisture loss is affected under different increasing temperature rates for the same range of the final upper constant temperature limit, indoor growers and the lower initial constant temperature level.

Accounting the lack of drying kinetic studies of hemp in literature, the present study aims to:  experimentally investigate the convective drying behavior and moisture removal of Cannabis sativa L. leaves for stationary and non-stationary drying conditions at a constant airflow velocity,  determine the kinetic profile that characterizes the convective drying of Cannabis sativa L. leaves by evaluating mathematical drying kinetic models. Drying rate versus time and moisture content is presented in Fig. 3. The drying process of hemp leaves at the examined drying conditions occurred entirely in the falling rate period, whereas no constant rate period was observed. The previous fact indicates that liquid diffusion is most likely the dominant physical mechanism, governing the water migration in Cannabis sativa L. from the interior to the surface of the leaves. Drying rate in time-varied temperature conditions resemble the drying rate behavior of the lowest constant temperature, since the initial applied temperature has been 40 ◦C. It is evident that higher constant drying temperatures and higher airdrying heating rates, are associated with increased drying rates and acceleration of the moisture removal, leading to shorter drying duration. Previous observations are in agreement with similar drying kinetic studies of various medical and aromatic plants submitted to hot air drying in the literature, reporting absence of constant-rate periods and similar trends between the applied constant drying temperatures. Global energy demand remains high even with the COVID-19 pandemic. Production of energy from fossil fuels has a negative impact on environmental health wellbeing and ecological balance. Many countries are requested to achieve challenging emissions reductions targets that will result in global net zero by 2050 and keep 1.5 ◦C within reach. To achieve these targets, investment in renewables is one of the solutions. Among renewable energy resources, biomass will play a vital role. Agricultural residues are lignocellulosic biomass considered to be major feedstocks for biorefineries. In many counties, hemp, Cannabis sativa L., is becoming a high-valued economic crop. It is a herbaceous plant grown up under different climatic conditions. Products from hemp include food and pharmacy. However, after processing two-thirds of starting raw materials become wastes, which are usually discarded or burned. Alternatively, hemp hurds/residues may be used as fuel, as they contain hemicellulose  and cellulose. Pyrolysis is a promising technology for converting hemp hurds into high-value products: biochar and bio-oils. Determination of kinetic and thermodynamic parameters for pyrolysis of a specific feedstock is essential for the design, optimization, and operation of the pyrolysis system.

For kinetics of biomass pyrolysis, Onsree et al. studied kinetics of corn residue pellets and eucalyptus wood ships pyrolyzed with heating rates of 5–15 ◦C/min using Kissinger-Akahira-Sunose  and Flynn-Wall-Ozawa  methods. They demonstrated that the kinetic parameters were a function of feed stock conversions. A discrete DAEM was also used to analyze kinetic parameters of pyrolysis of corn residues with high prediction accuracy. It can be seen that, by varying kinetic parameters, different biomass materials would have different pyrolysis behaviors. For thermodynamic analysis of biomass pyrolysis, Singh et al.investigated thermodynamic properties for pyrolysis of banana leaves at low heating rates of 10–30 ◦C/min and found that ΔH, ΔG, and ΔS fluctuated when the pyrolysis process proceeded. To the authors’ knowledge, very few studies on pyrolysis of hemp residues were reported, and conducted only at relatively low heating rates without considering thermodynamic properties. DAEM was rarely used in analyzing pyrolysis of hemp residues. Therefore, the current work aims to analyze kinetic and thermodynamic properties of pyrolysis of hemp hurds through the use of a discrete DAEM technique. Pyrolysis of hemp hurds was carried out from room temperature to 1000 ◦C at low and intermediate  heating rates. Decomposition of hemp hurds during pyrolysis was characterized and discussed. By the discrete DAEM, the accuracy of the model for predicting pyrolysis behaviors of hemp hurds was evaluated. Effects of different heating rate ranges on kinetic and thermodynamic properties of pyrolysis of hemp hurds were discussed. Information on kinetic and thermodynamic parameters is crucial for designing a pyrolysis reactor for hemp hurds, especially in large-scale production of biochar. The opinion about meat products and its impact on human health has become very negative in recent years. Dietitians pay attention to the high cholesterol and fat content or the amount of saturated fatty acids causing obesity and heart related diseases. According to the World Health Organization , total fat should supply less than 30% of energy from the diet and saturated fat should contribute less than 10%. The abundance of many chemical additives and smoking procedures are the main cancerogenic factors associated with the consumption of processed meat . At the same time, consumers in the developed countries tend to be interested in functional foods of vegetable and animal origins that, besides their role in providing basic nutrient components, are able to modulate the physiological system and prevent diseases. This goal is realized by adding various bio-active compounds such as n3 fatty acids, vitamins, selenium, dietary fibre or lactic acid bacteria, or simply by decreasing the animal fat content and/or exchanging it for more healthy fats . Lowering fat content or replacing the animal fat to develop healthier meat products may increase the production costs and change the products’ sensory properties .

Moreover, the consumers prefer and are willing to pay more for the product if it contains the ingredients coming from natural  sources . Hemp seed or the by-products obtained during oil production may be examples of such additives . Despite the fact, that it is one of the oldest crops cultivated all over the world, and is a valuable source of nutrients, it has been prohibited from cultivation because of the presence of psychotropic substances . Varieties containing up to 0.2% of THC  are approved by the European Union . The trend of a growing interest in hemp seed and food products containing hemp ingredients can be observed especially among vegans in many countries . Roasted seeds are a popular snack in China and hemp seed oil has been used for a long time in Russia and many other Eastern countries . There are also increasingly more various hemp products appearing on the market. They were used as food additives in breads, yoghurts, cookies or meat cutlets . Hemp seeds contain 27–30% of oil, 24–28% of protein, 20–34% carbohydrates, 10–15% insoluble fibre and 5.0–5.8% of mineral substances. The oil consists of 80–90% polyunsaturated fatty acids  including 50–70% linoleic  and 15–25% α-linolenic acid , and the n6/n3 ratio is 2.5–3.0. Hemp seeds contain wide range of minerals like calcium, magnesium, iron, manganese or zinc. The amino acids present in hemp seeds are comparable to those from egg or soy . In vitro and in vivo studies conducted by Girgih et al.  have shown that hemp seed peptides have the potential to be used as antioxidant and antihypertensive agents. Hemp proteins and hemp flour are by-products obtained from the oil extraction. They are also protein rich substances, trimming tray which could be used as an alternative to soy ingredients for preparing meat products. Moreover, functional products could be formulated using hemp additives because of the many health promoting ingredients present in hemp . To the best of our knowledge, there is no data in the scientific literature on the quality of meat products with hemp or hemp by-products. Therefore, the aim of this study was to verify if hemp seed, dehulled hemp seed, hemp flour and hemp protein could be used in the production of meat loaves and how they influence the products quality.The chemical composition of hemp additives and of all the manufactured variants of pork loaves is presented in Tables 2 and 3, respectively. The chemical composition of the Białobrzeskie hemp strain used in this study was similar to the composition of Finola hemp strain ; it contained less fat and more minerals compared to the commercially available hemp seeds  used by Worobiej, Mądrzak, and Piecyk .

Few publications show the quality of hemp flour or hemp protein which are available on the market. Hemp flour is prepared from defatted hemp seed, so it contains significantly less fat than the hemp seed, which was confirmed in our study . Svec and Hruskova  used hemp flour containing 32 g of protein and 8 g of fat in 100 g of a sample for bread production. A similar level of fat , but a lower amount of proteins  in commercially available hemp flour was reported by Korus, Gumul, et al.  and Korus, Witczak, et al. . The fat content in the hemp flour analysed by Worobiej et al.  contained 5.6 g/100 g of fat and 31.1 g/100 g of protein. The amount of fat may depend on the producer and the oil extraction method . Fibre content was high in all of the ingredients except the de-hulled hemp seed.The protein content was significantly higher in products with hemp seed, and the ash content was significantly higher in the products with hemp seed or de-hulled hemp seed. The fat content was comparable in all the samples with slightly higher amount in products with both hemp seed and de-hulled hemp seed. Moisture content was lower in all the meat loaves with various hemp additives compared to the control sample. The total fibre content in the meat loaves increased significantly thanks to the hemp additives. The results show the highest level of dietary fibre in the products with hemp seeds and hemp proteins . Fibre intake is associated with decreased constipation problems, obesity, colorectal cancer risk and diabetes , so it is worth increasing its content in meat products which naturally do not contain fibre. A significant increase was noted in the magnesium, manganese and iron content associated with the addition of every hemp ingredient . Magnesium plays a role in many regulatory processes in the human organism. Its deficiency is associated with depression and sleeping disorders . The Recommended Daily Intake for adults is 320–420 mg . The manganese requirement for an adult is 1.6–2.3 mg/day and it is required for proper reproductive system function, energy metabolism, metallo enzymes activity, antioxidant reactions regulation, etc. Iron availability from meat has been proven to be higher compared to the plant sources, but it is still only 15–30%, which means that any increase of the iron content may be treated nutritionally favourable. There are studies showing that even 180 g of pork per day does not fulfil the organism’s requirements. Moreover, meat intake increases non-haem iron availability .

The profile of the changing genes was comparable between tobacco and marijuana exposed cells.Many of the genes that were differentially expressed in TSC exposed cells are among those that have been typically observed to be induced by cigarette smoke [e.g., Nqo1,Esd,Hmox1,Cyp1a1 and Cyp1b1 ]. Moreover, the concentration response patterns support the assertion of initial metabolic responses,followed by responses to toxic insult  and secondary metabolism.Similar concentration response trends were noted in our previous toxicogenomics analysis of three different TSCs.Although very few studies have been conducted with marijuana smoke, Roth et al.  demonstrated the induction of cytochrome P450 genes following exposure of Hepa-1 cells to marijuana tar extracts. Furthermore, the authors showed that tar from marijuana cigarettes tends to be more effective than tar from tobacco at inducing Cyp1a1 gene expression. Since the cannabinoids present in marijuana are capable of acting through the aryl hydrocarbon receptor to induce cytochrome P450 enzymes,and Cyp1a1 is known to bioactivate procarcinogens such as PAHs,questions have been raised about the role of cannabinoids in augmenting the carcinogenic risk posed by marijuana smoke. The question becomes increasingly complex as the cannabinoids THC, CBD and CBN have also been shown to competitively inhibit Cyp1a1, potentially decreasing the production of carcinogens and curtailing negative consequences.In the present study, however, substantial differences in the expression profiles of cytochrome P450 genes between the two smoke types were not observed. The expression of Cyp1a1 following exposure to MSC was comparable to that following TSC exposure, and the microarray results were supported by RT-PCR.One of the differences in the xenobiotic metabolism responses for the two condensate types is that Hsp90 and Rras2 were only upregulated following MSC exposure. Despite these findings, Hsp90 has been previously observed to be induced following cigarette smoke exposure,dry rack cannabis and mutations in genes from the Ras family are known to be associated with cigarette-induced cancers .

The IPA Canonical Pathway most significantly affected by exposure to TSC was the NRF2-Mediated Oxidative Stress Response Pathway. In this pathway, the transcription factor Nrf2 is phosphorylated following exposure to reactive oxygen, and translocates to the nucleus where it binds to antioxidant response elements.It then activates the expression of detoxification and antioxidant genes that protect the cell against oxidative damage. Of the 192 genes in this pathway, 6–18 genes were perturbed by TSC at the various time points in a concentration dependent manner. The largest expression changes and number of genes were associated with the 6 h time point. Nrf2-regulated antioxidant genes have been shown to play an important role in protection against the toxic effects of tobacco smoke. Iizuka et al. showed that neutrophilic lung inflammation was significantly enhanced in Nrf2-knockout mice following cigarette smoke exposure.In addition, emphysema was observed 8 and 16 weeks following cigarette smoke exposure in the knockout mice, whereas no pathological abnormalities were observed in wild-type mice. Similarly, Gebel et al. confirmed the protective nature of Nrf2 against the development of emphysema in cigarette smoke exposed wild type mice versus Nrf2 knockout mice, and further investigated the relationships between Nrf2 and inflammation and cell cycle arrest.Comandini et al. conducted a meta-analysis of eight genomic studies on the mechanisms of smoke-induced lung damage in healthy smokers, COPD smokers and non-smokers.They found the Nrf2-mediated oxidative stress response Pathway to be the most significantly altered pathway in healthy smokers compared to non-smokers. In contrast, the Nrf2 pathway was not significantly differentially expressed in COPD smokers, indicating that Nrf2-regulated genes play a key role in protecting against the toxic effects of TSC. The authors suggest that the response of Nrf2- regulated genes may potentially be used as a biomarker for COPD susceptibility. In the present study, we found that the NRF2-Mediated Oxidative Stress Response Pathway is also an important component of the toxicological response to MSC.

IPA analyses identified it as one of the top five pathways for both time points and all concentrations of MSC, except for the lowest concentration at the 6 + 4 h time point.A comparison of the Nrf2 pathway at the 6 h time point for the highest exposure concentrations of TSC and MSC shows many similarities.The Nrf2 gene itself was up-regulated along with several basic leucine zipper family transcription factors such as Jun, Atf4, and Maff. In addition, several antioxidant and stress response proteins such as Nqo1, Prdx1, Hmox1, Sod, Txnrd1, Herpud1, Dnajb1/9 were up-regulated. Other studies have also noted that these genes are up-regulated following cigarette smoke exposure.However, a notable difference between the two condensates studied here is that Gclc and Gclm, the rate limiting enzymes in glutathione synthesis, were significantly upregulated by TSC,but were not statistically significantly affected in MSC exposed cells.Furthermore Gsta genes were up-regulated in TSC and Gstm genes were down-regulated in MSC exposed cells. These findings were further confirmed by the significant up-regulation of the Glutathione Metabolism Pathway in tobacco exposed cells at all times and concentrations and the significant down-regulation of this pathway in marijuana exposed cells, particularly at the high concentration at the 6 + 4 h time point. These results suggest that exposure to MSC elicits more severe oxidative stress than exposure to TSC. The relative difference between the two condensates to mount an antioxidant defense may account for the greater cytotoxicity of MSC observed here and in our earlier genotoxicity study, where it appeared that the acute toxicity of MSC prevented the manifestation of micronucleus induction.The assertion regarding the relative severity of oxidative stress induced by MSC and TSC is supported by published results from other studies. In a previous study, Sarafian et al. examined reactive oxygen species production and reduced glutathione levels as indicators of oxidative damage following exposure to marijuana smoke.They showed that exposure of human endothelial cells to marijuana smoke resulted in an 80% increase in ROS over control levels, and these levels were as much as three times higher than those resulting from tobacco smoke. Moreover, intracellular glutathione levels following marijuana exposure were lower than for tobacco, and were reduced by 81% relative to controls. The authors argued that the products produced by the pyrolysis of the cannabinoids were likely responsible for the oxidative damage.

The same authors also conducted preliminary studies with cultured lung alveolar macrophages from non-smokers and marijuana smokers, and found that marijuana smokers had lower levels of GSH than non-smokers, suggesting a decrease in GSH dependent oxidative defenses in habitual marijuana smokers.In a previous study, Sarafian et al. investigated the effects of marijuana smoke and tobacco smoke on apoptosis and necrosis in A549 lung tumor cells.They found that both tobacco and marijuana whole smoke inhibited Fasmediated apoptosis but promoted necrotic cell death. In addition, particulate phase smoke  from marijuana was a more potent inhibitor of Fas-induced caspase-3 activity than tobacco. In a later study, the authors also noted the decreased expression of Bax and caspase-8 in human small airway epithelial cells exposed to THC, which they suggest could have accounted for the previously observed suppression in Fas-mediated apoptosis.Although apoptotic pathways were not significantly perturbed following TSC exposure in our present study, Sarafian et al. and other investigators of tobacco smoke effects have found this to be a commonly disrupted pathway.It is suspected that the gene expression fold change cutoff of 2 used in the present study likely prevented a number of apoptotic genes from being included in the analyses.It is importantto note thatthe marijuana used for this study was obtained from a contracted supplier that provides marijuana for therapeutic use in Canada. It is grown under strictly controlled and documented conditions. Although this study has only examined smoke condensate from a single lot of marijuana, the quality control measures would be expected to minimise differences between marijuana harvests. The TSC used in this study was generated from cigarettes containing Virginia flue-cured tobacco, the type of tobacco typically contained in Canadian cigarettes. This is distinct from the mixed tobacco blends  typically found in American cigarettes.

Our earlier toxicogenomic examination of TSC from three Canadian cigarette brands containing either Virginia flue-cured or mixed tobacco blends failed to show any appreciable brand-driven differences in gene expression profiles elicited by in vitro exposures.Therefore, we contend that the similarities and difference between MSC and TSC noted in this study can be cautiously extended to other types of tobacco. Nevertheless, it should also be noted that some toxicogenomic studies have shown that cigarette brand  can have a significant effect on gene expression signatures elicited by in vitro CSC exposures,and moreover, many aspects of cigarette design  and smoking method  have been shown to influence the composition and toxicological activity of TSC .The pivotal role of protein in human health and the environment is becoming clear in several ways. Lack of protein is a key metric of malnutrition, while a dietary transition from primarily animal towards plant protein products is required to avoid biodiversity loss and climate change . However, diet is a cultural attitude that is difficult to change despite the potential health and environmental benefits . In this way, meat-eating consumers would prefer products that strongly resemble real meat , which triggers the search for more sustainable proteins that can be used to produce meat-resembling structures. Although successful plant-based meat substitutes, such as burger patties, are already available in the supermarkets of many countries, the development of whole-muscle cuts using plant proteins still remains a major challenge. Hemp is an unconventional crop with a broader spectrum of adaptation to colder and warmer conditions than other plants typical from moderate climates . Its increasing legalization and the diverse range of products that a hemp plant can produce has drawn the attention of a variety of industries . In addition, hemp grows prolifically with no pesticides and is good for soil phytoremediation, roll bench owing to its long roots growing and penetrating deep into the soil . Hemp seeds are particularly abundant in nutritionally relevant oil and proteins , with 25–30% oil, 20–30% protein, 30–40% fibre, and 5.0–5.8% of minerals on a dry basis  depending on genotype and growing factors . Hemp oil is extracted from the seeds by screw pressing, resulting in a residue after extraction ambiguously called meal or cake, with a protein fraction that mainly consists of globular globulins and albumins characterized by an amino acid profile that complements perfectly that from other plant proteins, such that from pea proteins . The amount of protein in the hemp seed cake/meal can be increased to over 60%  by removing 1) the carbohydrate-rich hull , and 2) the oil fraction through further pelletizing or using organic solvents .

Higher protein enrichment  can be attained by tandem alkaline extraction plus isoelectric precipitation , which still remains the most utilized aqueous extraction method to extract protein from oilseeds . It usually involves an alkaline solubilisation of the proteins, the removal of insoluble material by centrifugation and the isoelectric precipitation of the protein, followed by its separation by centrifugation . Nevertheless, the omission of aqueous extraction steps and, particularly, the omission of protein precipitation and final drying steps, can have a notorious reduction of the environmental footprint during protein fractionation, e.g., by decreasing the consumption of energy, water and chemical reagents, and the generation of chemical waste . With the amount of recovered protein as the functional unit , processes that have less refinement still have a lower negative impact than the conventional wet extraction method. In addition, AE-IP can result in differential extraction of storage proteins of different types , disrupt the native oligomeric state of proteins, and lead to thermodynamically favourable organized assemblies  that affect the functional properties of the resulting protein concentrates. Moreover, compared to lab-scale protein concentrates, industrial processes are performed under compromised, and often more complex, processing conditions to ensure economic viability. For example, processing at higher total solids  and temperatures  could explain the particularly poor solubility of commercial concentrates compared to their lab-scale counterparts . There is still, however, very little information about the technological functionality of commercial hemp protein concentrates. In addition, the effect of hemp protein industrial-scale enrichment technologies on the anisotropic structuring behaviour of hemp protein concentrates has not been reported.

McQueeny et al.  showed adolescent girls had larger amygdalae and increased internalizing symptoms when compared to both control and marijuana using boys. Moreover, certain behavioral problems have also been linked to prenatal marijuana exposure in girls, but not in boys.Recent neuroimaging work suggests that young female users may be vulnerable to marijuana-induced alterations in brain volume, given suggestions of greater prefrontal cortex volumes and relatively poorer levels of executive function.Alcohol is similarly disruptive to females’ cognitive function and regional brain morphology,and it has long been recognized that females are more vulnerable to psychomotor sensitization with psychostimulant exposure.Preclinical data are somewhat stronger and indicate that female adolescents are particularly vulnerable to the effects of long-term THC administration on the CB1 receptor system in multiple brain regions, including the prefrontal cortex, striatum, and periaqueductal gray.A recent study of THC in mid-adolescent rats during the period of drug administration and following abstinence indicated greater sensitization of THC-induced locomotor depression in females versus males. Moreover, high doses resulted in increased anxiety-like behaviors during THC administration, particularly in females,although a general tendency is for females to experience greater anxiolytic effects of the drug. Glutamate is critically important in the neuroplasticity that accompanies the transition from drug use to abuse.Under conditions of extreme trauma or stress, its release is associated with neurotoxicity and cell death.Endocannabinoids block glutamate release under such conditions,which could lead to neuroprotection. However, the concomitant observation of high mIns levels argues against this interpretation. Given that mIns is considered to be a glial marker, high levels would be associated with gliosis as well as white matter injury as occurs in the context of neural injury. High mIns concentrations have been observed in early dementia, in frank Alzheimer’s disease,drying cannabis as well as in abstinent methamphetamine users, although this latter observation was in the frontal lobes.

This pattern is intriguing given that deficits in learning and memory represent one of the robust areas of reported cognitive dysfunction in marijuana users.Although our data analyses do not suggest that female marijuana users in this sample are more vulnerable to cognitive impairments,this is a relatively young and high functioning sample. It may be that frank behavioral deficits will emerge more strongly in females over time as chronicity of use progresses. We hypothesize, too, that we may have observed altered NAA levels had we also measured frontal concentrations of each metabolite. Even though our statistical analyses do not show any significant effect of alcohol, it is important to consider the possibility of an underlying biological interaction between the two substances. Male marijuana users in this study had the highest levels of alcohol use, but did not show significant neurochemical alterations relative to controls. Females showed the greatest apparent impact of marijuana use on Glx and mIns, but in the context of lower levels of alcohol use. These findings could suggest a neuroprotective effect in individuals who use both marijuana and alochol, as described by others.Alternatively, previous work has shown greater levels of Glx in the anterior cingulate of chronic alcohol users relative to controls.Considering this, taken together with the findings of the present study, it is possible use of the two substances together may drive metabolite concentrations to “normal” levels via opposing processes, as has also been suggested by others in the context of brain morphology.Differences in metabolic function in heavier versus lighter alcohol users can also impact the conversion of acetate into glutamate.It is possible, then, that the male marijuana users in this study who were heavier alcohol users as compared to females, demonstrated differences in glutamate metabolism, contributing to the observed sex difference. However this assertion is only speculative.

While our data do not fully support these conclusions, the issue of alcohol use in the context of marijuana use requires careful examination in future studies. Sex but not group-related effects were also observed in total choline estimated concentrations.Independent of marijuana use, males showed higher estimated concentrations of tCho compared to females. Numerous choline-containing compounds contribute to the tCho signal measured in this study, complicating the interpretation of this sex difference. For example, phosphatidylcholine plays an important role in the phospholipid bilayer in cell membranes, and choline is essential in the formation of the neurotransmitter acetylcholine. Generally speaking, increases in choline signal in the brain have been demonstrated in cases with pathology .While this study has numerous strengths, it is not without limitations. Given time constraints on the scanning protocol, glutamate and glutamine could not be resolved separately from the acquired spectra. Even though this is a common problem, especially at lower field strengths,it poses limitations on the interpretation of the data because of the different biochemical functions of these metabolites. After release of glutamate into the synapse, cycling between glutamate and glutamine occurs in glial support cells in order to maintain high SNR in glutamatergic neurons, and to protect against adverse excitotoxic effects.Resolution of the glutamate versus glutamine signals would allow stronger interpretations to be offered regarding the meaning of the low levels observed in female users. Given that more extensive spectroscopy scanning is time intensive and requires higher field strengths to be conducted most efficiently, these findings together with other recent studies  suggest that a more in-depth examination of neurochemical metabolism within frontostriatal circuits in heavy marijuana users is warranted. Another limitation of the study is the constrained spatial resolution of the spectra. It would be beneficial to examine additional brain structures, however spectral resolution was chosen over spatial resolution for the current study. Moreover, while the sample sizes are small in relation to the reported group by sex interactions, numerous reports exist which demonstrate a similar a pattern of sex-effects, where females who use or are exposed to illicit substances  are differentially affected.Finally, we did not measure urine or hair concentrations of THC, so it is possible that participants in the study used less marijuana than they reported. We find this to be unlikely given the level of detail that was provided about habits surrounding use in our direct interviews, participants’ consistent reporting regarding their symptoms of DSM-IV marijuana dependence, and concomitant evidence of neurocognitive impairment consistent with marijuana exposure.

Further, the majority of previous studies that collected urine/hair data and quantified cannabinoid concentrations did not show significant associations between these concentrations and brain metabolite data, suggesting such data are perhaps not necessary for this type of analysis in the presence of detailed clinical assessments. Nonetheless, the study would be strengthened by the ability to compare brain metabolic data with cannabinoid levels as obtained by blood, hair or urine analysis.A long-standing observation in clinical and epidemiological research into substance use has been that users of one drug typically do not limit their use to a single substance.For example, alcohol and tobacco are commonly used by the same person and often in the same setting, as are tobacco and marijuana. Though the synergistic effects of these particular drugs have been suggested as a potential explanation,another interesting possibility is that individuals have an underlying liability to drug use within and across different pharmacological classes. Support for this notion has been shown for both licit and illicit drugs in a variety of populations and drug use phenotypes.As poly-substance use is associated with problematic use and reduced treatment efficacy,identifying informative precursors to the onset of abuse and dependence remains a priority. Among the variety of factors that have been examined as a nearly indicator of later, more problematic use patterns, how someone experiences a drug,is one of the most interesting.Factor analytic studies of these experiences frequently yield two main factors: pleasant or positive and unpleasant or negative.Positive subjective experiences often include euphoria, relaxation, and feeling less inhibition. Negative subjective experiences include nausea, difficulty inhaling, dizziness and sadness. Though weakly correlated,users of a drug sometimes report both positive and negative experiences. Alcohol, tobacco, and marijuana are the most commonly used licit and illicit drugs. Studies examining the subjective experiences to these drugs have generally found that how a person responds to a particular drug is predictive of more problematic use of the same drug.

For example, dependent cigarette users more frequently endorse positive experiences than regular smokers and moderate-to-heavy drinkers report experiencing greater stimulant-like effects to alcohol than lighter drinkers.A similar relationship has been demonstrated for marijuana use.Although results are mixed, negative experiences to tobacco and marijuana have also been positively associated with problematic use.For alcohol consumption, low levels of response, primarily measured using negative subjective effects, have been associated with an increased risk of an alcohol use disorder  as lower thresholds to the sedative effects of alcohol protected against developing abuse later in life.A handful of previous studies have suggested that subjective experiences for different drugs may share a common etiology.In particular, subjective experiences to a variety of drugs are correlated and can predict levels of involvement for substances in other pharmacological classes. This observation has been shown for pleasurable experiences of alcohol and tobacco where both drugs were predictive of current alcohol use in a college aged sample.Further, marijuana use has been shown to increase a sense of “liking” among non-smokers whereas alcohol has no effect on the subjective experiences of cigarettes.Lastly, greater rates of alcohol dependence and illicit drug use have been observed among high marijuana users as defined by greater rates of sensitivity to positive and negative subjective experiences.Though additional studies are needed, ebb flow these cross-drug results indicate that how a person responds to a drug is predictive of how they will respond to other drugs. In this report we detail findings from a study of subjective experiences to alcohol, tobacco, and marijuana in a sample of young adults participating in the Colorado Center for Antisocial Drug Dependence. Subjective experiences were collected from both clinical and community participants using a questionnaire developed by Lyons et al..Our analyses were designed to address three questions. First, how do positive and negative subjective experiences across alcohol, tobacco, and marijuana compare? Second, to what extent do subjective experiences to alcohol,tobacco, and marijuana overlap? Lastly, to what degree do subjective experiences to one drug associate with more problematic use behaviors for a different drug?Participants were drawn from the Colorado Center on Antisocial Drug Dependence [CADD] and consisted of 3853 participants  between the ages of 11 and 30 years old and included both community and clinical participants.

Our community-based sample  was drawn from those participating in the Colorado Twin Registry,Colorado Adoption Project,with clinical controls drawn from the Colorado Adolescent Substance Abuse Family Study.Our clinical sample  was drawn from adolescents in treatment for substance abuse and delinquency as a part of the ASA study.Additional clinical participants were drawn from an adjudicated sample from the Denver metropolitan area.Siblings of the clinical subjects  were also included. All participants in the current study met one or more of the following criteria:  they had consumed at least six drinks in their lifetime,  had used tobacco daily for at least one month, or  had used marijuana six or more time in their lifetime.Patterns of alcohol, tobacco and marijuana use, abuse and dependence symptomatology were collected using the Composite International Diagnostic Interview-Substance Abuse Module.Abuse and dependence status as defined by the Diagnostic and Statistical Manual of Mental Disorders  was determined using scoring algorithms based on whole life substance related problems. Retrospective subjective experiences were collected using a 23- item questionnaire developed by Lyons et al..The original Lyons questionnaire was comprised of 23 items. As discussed in Zeiger et al.,due to the CADD interview length the original Lyons questionnaire was shortened after wave 1; a factor analysis was conducted on the Lyons questionnaire and 10 items with lower or mixed loadings were dropped. Subsequently, most subjects received the shortened 13-item questionnaire, thus these analyses were conducted on the 13-item response set from all subjects The 13-items included: social, mellow, creative,top of the world, increased sex drive, energetic, dizzy, nauseous, drowsy, lazy, unable to concentrate, out of control, and guilty. Participants were asked “in the period shortly after you used  did it make you feel…”? Responses were scored as present  or absent  and the item scores summed to make the positive and negative scales.

Despite the low number of asthma respondents, the self-reported asthma prevalence rate of adolescents in this study  was similar to that reported  by the Ontario Asthma Surveillance Information System,which uses a validated health administrative data case definition to capture asthma with 84% sensitivity and 76% specificity. Secondly, the cross-sectional design of the survey is a major study limitation in assessing causal relation of asthma and smoking. It is unknown from this study whether adolescents with asthma smoked e-cigarettes more often or if smoking e-cigarettes contributed to the risk of asthma. Thirdly, asthma was self-reported and it not clinically confirmed. Self-reported asthma may over or under represent actual prevalence of asthma. Furthermore, many studies  that examined the relationship between asthma and smoking did not separate severe or “uncontrolled” asthma from those with well-controlled mild to moderate asthma. The effect of smoking on adolescents with severe or uncontrollable asthma may be different than on those with mild to moderate asthma. The definition of smoking used may influence the study findings. We classified smoking for cigarettes, marijuana and water pipes as smoking one or more time over the past 12 months or ever for e-cigarettes. This definition includes those who smoke regularly but also adolescents who experiment with the various types of smoking. This classification of smoking has been used previously in studies using the OSDUHS data-set. We conducted additional analyses using another method of classifying smokers reported by Wong and colleagues. In this method a regular smoker is defined as smoking more than 100 cigarettes in their lifetime and any cigarettes in the past month. Using this method the results and point estimates remained very similar. Given this method of classification was only available for cigarettes, we opted to retain the ‘any cigarettes over the past 12 months’ method to ensure measurement correspondence with the other types of smoking.

Nevertheless, results suggest that adolescents with asthma are at least experimenting with e-cigarettes or any type of smoking more often than their peers without asthma, which may lead to higher smoking rates later in life. Finally, we were unable to adjust for parental smoking or parental history of asthma as these data were not collected by the survey. Having a parent who smokes may relate to the respiratory health of children,pot for growing marijuana but it also increases the odds of smoking for adolescents. While information on parental smoking is not available in our data, further research should examine the association between parental smoking and asthma for all types of smoking. This paper adds discussion to the question of whether adolescents with asthma would be less likely to smoke cigarettes, water pipes, marijuana or e-cigarettes. Our study findings suggest that adolescents with asthma had a significantly higher odds of smoking e-cigarettes or any substance. This may suggest a lack of knowledge of the potential harmful long term effects of smoking ecigarettes or a general perception that e-cigarettes are “safer” than tobacco cigarettes. While recent research has suggested that ecigarettes are less harmful than tobacco cigarettes, the long term effects are still unknown. Furthermore, a recent study reported that e-cigarette usage for adolescents increases the odds of smoking tobacco cigarettes in adulthood by six times [OR:6.17; CI:3.3e11.6], suggesting that e-cigarettes may be used as a gateway among teens. Public health campaigns and education should target adolescents and especially those with asthma to raise their awareness of the risks  of all types of smoking. Results from this study suggest that adolescents with asthma are not more likely to be smoking cigarettes, water pipes or marijuana than those without asthma. As the means  of smoking change, how adolescents can smoke,presents new challenges in relation to adolescent smoking and asthma. This study found that adolescents with asthma were more likely to smoke e-cigarettes than those without.

The results did not change when we included any type of smoking. Our study findings can be used to target the adolescent asthma population for smoking prevention and education campaigns and to raise their awareness of the risks associated with smoking in general. Although recent studies have reported that adolescents with asthma are more likely to smoke cigarettes or water pipes, this does not appear to be the case in Ontario, after adjusting for confounding variables. While this is encouraging, our study suggests that e-cigarettes are now popular among youth with asthma. Work should continue with anti-smoking and prevention campaigns to try and further reduce all smoking rates for adolescents, with an emphasis on the unknown and potential serious long term risks associated with e-cigarettes or alternative types of smoking.Adolescence is a unique developmental period characterized by major physiological, psychological, and neuro developmental changes. These changes typically coincide with escalation of alcohol and marijuana use,which continues into early adulthood.The comorbid use of alcohol and marijuana among teens continues to subtly rise as perception of harm declines. Fifty-eight percent of alcohol drinking adolescents report using alcohol and marijuana simultaneously,,45% of youth endorse a lifetime prevalence of marijuana use by the 12th grade, and 22% of these youth endorse use in the past 30 days .The adolescent brain undergoes considerable maturation, including changes in cortical volume and refinement of cortical connections.These neural transformations  leave the adolescent brain more susceptible to potential neurotoxic effects of substances.Although overall brain volume remains largely unchanged after puberty, ongoing synaptic refinement and myelination results in reduced gray matter and increased white matter volume by late adolescence.Cortical gray matter follows an inverted U-shaped developmental course, with cortical volume peaking around ages 12–14.The mechanisms underlying the decline in cortical volume and thickness are suggested to involve pruning and elimination of weaker synaptic connections, decreases in neuropil, increases in intra-cortical myelination, or changes in the cellular organization of the cerebral cortex.In contrast, white matter development generally is characterized by linear volume increases driven by progressive axonal myelination.

These processes refine motor functioning, higher-order cognition, and cognitive control.Studies show alterations in white matter integrity in adolescent marijuana users compared to non-users, particularly in fronto-parietal circuitry and pathways connecting the frontal and temporal lobes.Altered cortical morphometry has also been observed in adolescent marijuana users, with marijuana-using adolescents having larger cerebellar volumes than non-users,thinner cortices in prefrontal and insular regions, and thicker cortices in posterior regions when compared to controls.Structural neuro imaging studies have also examined whether structural brain alterations were present before onset of marijuana use.Notably, orbitofrontal cortex  volumes at age 12 predicted initiation of marijuana use at age 16 when controlling for other substance use. Regional volume vulnerabilities may increase risk for initiation and maintenance of marijuana misuse. This study builds on previous work by our laboratory examining the acute and longer-term impact of adolescent marijuana use on cortical thickness pre- and post 28-days of monitored abstinence from marijuana.We found increased temporal lobe thickness estimates in adolescent heavy marijuana users,and negative associations with cortical thickness and lifetime marijuana use both acutely and following prolonged abstinence from marijuana. It is unclear if such structural alterations of the cerebral cortex persist into young adulthood. The aim of this prospective study was to identify differences in cortical thickness between adolescent heavy marijuana users and control adolescents with minimal substance use histories assessed at three independent time points.We hypothesized that those individuals who initiated heavy marijuana use during adolescence would show thicker cortices over time compared to our control teens by young adulthood in frontal and temporal brain regions.This study looked at cortical thickness estimates at three independent time points  in adolescent marijuana and alcohol users compared to controls with limited substance use histories. We found significant between group differences in cortical thickness estimates after controlling for lifetime alcohol use. MJ +ALC demonstrated increased cortical thickness estimates in all four lobes of the brain, bilaterally.

Notably, 18 of 23 regions in which differences were observed were in the frontal and parietal cortex. Positive dose-dependent associations were identified in temporal brain regions,container for growing weed as cumulative marijuana use from ages 16 to 22 was associated with thicker cortices in inferior temporal and entorhinal cortex. Several negative associations were observed with lifetime alcohol use, as more alcohol use reported was associated with thinner cortical estimates in all four lobes. It is important to detail how these findings compare to our previous work with a similar sample, as we found both similarities and differences from our cortical thickness study in which adolescent marijuana users were observed pre- and post 28-days of monitored abstinence.In Jacobus et al.,increased thickness estimates in our marijuana users  was found in the entorhinal cortex compared to matched controls. Similarly,the present study found increased thickness estimates in our user group compared to our controls, and findings were more widespread and noted in all four lobes of the brain. The present study also found more lifetime marijuana use was associated with increased thickness in the entorhinal cortex, a region rich in cannabinoid 1  receptors and important for learning and memory.However, dose-dependent bivariate correlations were different in that previously we saw increased marijuana use associated with thinner cortices and increased alcohol use associated with thicker cortical estimates at age 17, pre- and post monitored abstinence. Our dose-dependent associations in the present study suggest otherwise. We found increased lifetime marijuana use reported associated with thicker cortical estimates and increased lifetime alcohol use reported associated with thinner cortices.This may reflect several points recently discussed by Filbey and colleagues  in the literature, including methodological issues,the present study assessed substance independently over the course of three years compared to 28-days at age 17;  age and maturational bias, correlations in the present study reflect associations following many years of substance use and potential for interference with complex neuro developmental processes;  changes in marijuana and alcohol use patterns, as individuals in the present study remain relatively chronic in their marijuana use over time but subtly increase in their alcohol use; and  possible interactions with pre-existing vulnerabilities that are present at age 17,but likely changes as the individual continues to chronically use substances and increase in age.Lopez-Larson and colleagues cross-sectionally investigated cortical thickness in adolescents ages 16–19 years, with heavy marijuana use histories.

They found decreased thickness in frontal regions and the insula, along with increased thickness in lingual, temporal, and parietal regions. The present study found increases in thickness in parietal, temporal, and occipital cortices, consistent with work by this team. The mechanism by which marijuana may alter the neural architecture and plasticity of the brain is undetermined. The endocannabinoid system plays a role in neuromaturational processes and modulates neurotransmission for several neurotransmitter systems .Interference with this system due to marijuana, or tetrahydro cannabinol  administration, likely causes a cascade of neuronal events  that changes brain structure and function,and thereby neurocognitive processing,emotional regulation and reward processing,and propensity for psychiatric comorbidities and addiction.It is unclear how associations with marijuana use and cortical thickness remodeling may be unique compared to alterations in macrostructural volume.Studies suggest that volume changes are driven by changes in surface area  whereas others suggest thickness as one ages,however relationships between these metrics are likely dynamic across the lifespan and represent different neuromaturational mechanisms at different stages of life and disease. Changes in regional brain volume associated with marijuana use have varied, as some have observed decreased volume  and others have identified macrostructural volume increases in CB1-dense brain regions such as neocortex, amygdala, striatum, hippocampus, and cerebellum.In reward-network regions specifically, such as the orbitofrontal cortex,a recent examination by Filbey and colleauges, found decreased orbitofrontal cortex  volume in heavy marijuana users compared to controls, and increased structural and functional connectivity within the OFC network. Lorenzetti and collages,did not find OFC differences in their sample of heavy marijuana users, but did see smaller hippocampus and amygdala volumes. Cheetham et al.  found that smaller OFC volume pre-initiation of marijuana use  predicted progression into use four years later.Taken together, findings underscore that alterations in cortical metrics are likely dynamic and influenced by age, pre-existing vulnerabilities, and exogenous factors such as marijuana use. Continuing to study associations between cortical metrics and substance use is important given estimates have been linked to cognitive functioning in several studies in our laboratory and others .

However, in marijuana users, the inverse effect has been observed. For instance, in a study by Terracciano et al.,marijuana users exhibited greater “excitement-seeking” and “activity”compared to non-users. The authors postulated that these facets of extraversion may contribute to marijuana use. Reports of marijuana use may also be more highly associated with extraversion due to the more communicative personality traits  implicated in admission of illegal activity. However, in line with the studies mentioned above, the more robust effect is likely the similarly of the extraversion “excitement-seeking” facet, and sensation-seeking, which is a well established risk factor for drug use.Together with our findings of greater openness in marijuana users, we speculate potential specificity of personality traits in different substance using population. This underlines the need to characterize substance-using populations relative to each other.Additionally, given the widely accepted association between novelty-seeking and sensation seeking in marijuana users,it may be through extraversion that these risk factors lead to substance use disorders.Thus, greater sensation seeking in drug abusers would suggest that extraversion could be a risk factor  as others may suggest in other SUDs. In addition to openness, other factors that discriminated marijuana users from nicotine users in our study have been linked to neurological systems responsible for appetitive-approach behaviors.Recent imaging work has shown specific brain mechanisms associated with similar traits including motivation, optimism, and enthusiasm. For example, DeYoung et al. showed that extraversion scores covaried with medial orbitofrontal cortex volume, which has also been shown to be altered in long-term marijuana users.Agreeableness was positively associated with retrosplenial PCC,mobile vertical rack which is implicated in altered sensory awareness in addiction.

Similarly, genetic mechanisms have also been associated with personality traits. For instance, COMT Val158Met allele has been posited to modulate extra version.Together, these results suggest potential mechanisms for the association between these personality traits and marijuana use. The current findings of greater openness in marijuana users also fit within the framework put forth in studies of marijuana use motives. Specifically, out of five putative motives for marijuana use,highest endorsements have been reported for those that require openness, such as the enhancement motive,followed by social  then expansion  motives.Future studies are needed to directly examine this relationship.However, altogether, these findings suggest that the openness personality factor is a risk marker for engagement in marijuana use  as a means to expand on one’s life experience .Delta-9-tetrahydrocannabinol,the main psychoactive component of marijuana, binds to CB1 cannabinoid receptors in the brain. Endogenous cannabinoids are involved in the regulation of emotional responses, including mood, anxiety, and aggression,and laboratory studies support an acute impact of THC on mood and emotion.CB1 receptor expression is highest during adolescence, dropping thereafter into adulthood with the most pronounced decreases observed in limbic regions critically involved in emotion regulation.Thus, adolescent exposure to THC may have lasting consequences on the developing brain that specifically impact the regulation of emotion. Some support for this comes from structural imaging studies showing volumetric differences in adolescent marijuana users compared with controls in limbic regions,including the amygdala, hippocampus, and insula.For example, larger amygdala volumes were observed in female marijuana users compared with controls, which was further associated with depression and anxiety symptoms.Other work has observed that marijuana users have differences in cerebral blood flow and resting connectivity compared with controls in brain regions involved in emotion, including the insula and temporal cortex.Together, the evidence supports an association between marijuana use during adolescence and an alteration of the neural systems supporting emotion regulation. However, to date only one study has investigated the effects of marijuana use on brain functioning during an emotion task. This study of adult heavy marijuana smokers found decreases in anterior cingulate and amygdala activation during the viewing of masked affective faces, suggesting a difference in the way marijuana users process emotional information.

To date, no studies have investigated how the use of marijuana specifically during adolescence impacts these processes; thus, one goal of the current study was to address this gap by investigating brain functioning during emotion arousal in 17–22 year-old heavy marijuana smokers who began their use earlier in adolescence. Furthermore, although there is evidence for a prospective relationship between early marijuana smoking and later negative emotionality,the literature regarding the intermediary brain processes in this relationship has been less clear. The work reviewed above has been crosssectional, and consequently, inferences cannot be made regarding causal relationships among history of marijuana use, brain functioning, and negative affect. Therefore,this study uses a prospective design to better address the nature of the relationship and to investigate whether emotion-related brain function in late adolescence/emerging adulthood mediates a relationship between prior marijuana use and later emotional functioning. We investigate two facets of emotional functioning, which are grounded in the temperament and personality literature—negative emotionality and resiliency.Negative emotionality is the propensity to experience depressed mood, anxiety, and irritable anger. Resiliency is the ability to flexibly adapt one’s level of control—in either direction—in response to the demands of the environment. It involves thoughtful, deliberate control of behavior in challenging or stressful circumstances and freer expression in circumstances where it is appropriate.This type of self-regulation is a critical aspect of emotional regulation.Note that the construct of resiliency is not directly related to the idea of resilience to adversity. Rather, resiliency has its conceptual roots in the temperament-based work of the Blocks,who identified the related construct of ego resiliency. Using a prospective, longitudinal design, we investigate negative emotionality and resiliency measured at three time points:  at the approximate age when the heavy marijuana smokers initiated use ;  within one year prior to participation in the functional magnetic resonance imaging  study of emotion arousal ; and  approximately three years after participation in the fMRI study.Information on occasions of marijuana use was collected prospectively on an annual basis from age 11 up to the time of participation in the fMRI study.

This design allows us to investigate the impact of marijuana use during adolescence on the development of negative emotionality and resiliency and on emotion-related brain function, and to investigate whether emotion-related brain function mediates a relationship between prior marijuana use and later emotional functioning.Forty participants were selected from an ongoing fMRI study of adolescents and young adults recruited from the Michigan Longitudinal Study.The MLS is an ongoing, prospective community-recruited study of families with parental alcohol use disorder  along with a contrast sample of families without AUD drawn from the same neighborhoods.All parent diagnoses were ascertained by a clinical psychologist based on Diagnostic Interview Schedule – Version 4  and established at time of recruitment and via multiple face-to-face diagnostic assessments ofthe parents over the course of the youth’s life. Families in which the target offspring exhibited signs of fetal alcohol syndrome  were excluded from the original ascertainment. Exclusionary FAS characteristics included prenatal or postnatal growth retardation or both, central nervous system involvement, and characteristic facial dysmorphology.From the time of enrollment, all family members are assessed at 3-year intervals with an extensive psychosocial battery of measures assessing temperament, behavioral symptomatology, IQ, school performance, social interaction, etc. During the 11–26 year-old period, all offspring are also assessed annually on substance use and problems. Full details on the prospective assessment and data collection protocol in the MLS can be found elsewhere.One hundred and thirty 17–22 year old offspring from the MLS have completed an emotion arousal task during fMRI.Exclusionary criteria for the fMRI study included neurological, acute, uncorrected, or chronic medical illness, current or recent  treatment with centrally active medications, or history of psychosis in first-degree relatives. The presence of most active primary Axis I disorders was also exclusionary; this did not include unmedicated mood and anxiety disorders, antisocial personality disorder, or substance use disorder. The goal of this work was to investigate the impact of heavy marijuana use during adolescence on later emotional functioning, as well as potential brain function mediators of this effect.

Using a prospective design, we investigated two outcomes related to emotional functioning: negative emotionality and resiliency. We found that heavy marijuana users did not differ from controls in emotional functioning early in adolescence when marijuana use was initiated, whereas in late adolescence/early adulthood, heavy users had more negative emotionality and less resiliency than controls. To investigate the impact of adolescent marijuana use on emotion-related brain functioning, we compared neural responses to emotional words in heavy marijuana users and controls. Compared with controls, heavy users had less activation in emotion processing and integration regions,vertical grow rack including the right insula, prefrontal cortex, and occipital cortex during the viewing of negative words, and in a region involved in attentional control  during the viewing of positive words. Amygdala activation was lower to both negative and positive words in heavy users compared with controls. Further, we found heightened activation to positive words in the dorsolateral prefrontal cortex among heavy users. Activation in prefrontal cortex during the viewing of negative stimuli mediated an association between marijuana use and both negative emotionality and resiliency at follow-up. Activation in visual association regions of the occipital cortex mediated an association between marijuana use and later resiliency, but not negative emotionality.Heavy marijuana users scored higher on negative emotionality than controls at the approximate ages of 20 and 23, whereas groups did not differ at approximately age 13, when heavy users initiated use. Furthermore, exploratory analyses revealed that negative emotionality decreased from early adolescence to young adulthood in controls—consistent with normative changes —but not in heavy users. Importantly, we observed an association between greater lifetime marijuana use occasions and higher negative emotionality at age 20, after controlling for early levels  of negative emotionality. These findings are in line with other longitudinal work showing that adolescent marijuana users had increased depression, anxiety, and suicidality in young adulthood, but marijuana use was not associated with premorbid differences in negative affect.Thus,the current results add to previous work supporting an association between early marijuana use and later negative affectivity.

We also investigated the impact of marijuana use on resiliency, as self-regulation plays a critical role in emotional functioning .We found no difference between groups inresiliency at the age of marijuana initiation, whereas differences emerged in late adolescence/early adulthood, with lower resiliency in the heavy use group. Although conceptualized as a temperament/personality trait, evidence indicates that resiliency improves throughout adolescence and into adulthood in healthy individuals.Here we found that resiliency increased over time in controls but notin heavy users. Furthermore, lifetime occasions of marijuana use was negatively correlated with resiliency, even after taking into account early level of resiliency. Resiliency is inversely related to depression and internalizing problems in children  and emerging adults,and positively related to effective social interaction  and social status.A reciprocal longitudinal relationship has been demonstrated between resiliency and positive emotionality from adolescence to early adulthood, as well as with the effective management of negative emotions.It is possible, therefore, that adolescent marijuana use may impact emotional functioning partially through an influence on resiliency; however further work in a larger sample is required to determine these longitudinal relationships. A central goal of this study was to characterize the neural mechanisms through which adolescent marijuana use exerts its effects on later emotional functioning. We found that activation in the right prefrontal cortex to negative words mediated the association between heavy marijuana use and both negative emotionality and resiliency at follow-up. Specifically, activation in the right middle frontal gyrus and dorsolateral superior frontal gyrus was lower in heavy users than controls, an effect that was associated with decreased resiliency and increased negative emotionality at follow-up. This area of the prefrontal cortex has been referred to as the caudal dorsolateral prefrontal region  and is closely connected with motor and supplementary motor regions.Prior work has found activation ofthe caudal dlPFC and associated regions during the reading of high-arousal emotional words.The supplementary motor and premotor regions are important for emotion processing and empathy  and may regulate approach-withdrawal tendencies to emotional stimuli by integrating limbic and motor responses.A recent meta-analysis found that activation in these regions decreased to negative stimuli in alexithymia, a trait characterized by difficulties with experiencing and processing emotions.The current findings suggest that heavy marijuana use during adolescence may impact caudal dlPFC functioning, impairing the processing and integration of emotional stimuli and lead to increased negative emotionality.

Here we document what we believe is the first known case of pulmonary mucormycosis associated with medical marijuana use.A 66-year-old man presented to the emergency department with a two-month history of shortness of breath, cough, rust-colored sputum, night sweats and a 20 pound unintentional weight loss. He had a history of poorly controlled type 2 diabetes mellitus and chronic lower back pain. He was a 1-pack-per-day smoker for thirty years. Three months prior to presentation, he had started smoking medical marijuana for relief of his chronic back pain. The marijuana was obtained from a medical dispensary. He previously worked as an auto mechanic but had retired six months prior to presentation. On physical examination, respiratory rate was 24 breaths per minute with an SpO2 of 98% on high flow oxygen.There were bilateral coarse breath sounds on pulmonary examination. White blood cell count was 17.3 × 103 /μL. Blood glucose was 348 mg/dL and hemoglobin A1c was 10.0%. Plain film chest x-ray showed multiple large oval opacities in both lungs. Computed tomography of the chest showed multiple bilateral large ground glass opacities with surrounding areas of consolidation. Infectious workup including blood, urine and sputum cultures was negative.Vasculitis and autoimmune workups were negative. Bronchoalveolar lavage cultures grew normal oral flora. The patient was treated with a broad spectrum antibiotic regimen including vancomycin, piperacillin-tazobactam and levofloxacin without clinical improvement. The patient was intubated and underwent video-assisted thoracoscopic surgery on hospital day 7. The lungs were noted to have areas of severely friable and inflamed lung parenchyma and pleura.Culture of the biopsied lung tissue grew Rhizopus species.He was started on liposomal amphotericin B and micafungin. His oxygen requirements decreased and he was extubated on post-operative day 12.

He received two weeks of parenteral amphotericin and was then transitioned to oral posaconazole after clinical improvement. Repeat CT one month later showed stable size of the cavities and continued improvement of the patient’s respiratory function. He was readmitted two months later with hemoptysis which stopped spontaneously. One month after discharge from the second hospitalization, he died of massive pulmonary hemorrhage despite continued therapy with posaconazole.Mucormycosis is an angioinvasive disease caused by species of the order Mucorales,grow cannabis most commonly of the genera Rhizopus, Mucor, and Rhizomucor. Mucormycosis most commonly manifests as rhino-orbitalcerebral infection but may also present as pulmonary, cutaneous, gastrointestinal, central nervous system or disseminated infection. Disease is typically seen in immunocompromised patients, including those with Diabetes mellitus, particularly in the setting of diabetic ketoacidosis.High plasma glucose and iron concentrations upregulate expression of glucose-regulated protein 78,a heat shock protein present on host endothelial cells. CotH is a fungal spore coat protein present in pathogenic Mucorales species and acts as the fungal ligand which binds to GRP78, inducing endocytosis and leading to angioinvasion. Mucorales are widespread and are can be found where humid organic matter is exposed to heat, such as in composting vegetation or rotting fruit. Marijuana, though known to contain Mucorales species, has not previously been associated with mucormycosis. Like all Zygomycetes, Mucorales produce spores that are released into the environment where they remain airborne and may eventually gain entry to the body via inhalation. Definitive diagnosis is made by histopathological, cytopathological, or direct microscopic visualization in affected organs. Hyphae of mucorales species are easily damaged during biopsy or tissue preparation and thus microscopic or histopathological examination is usually more useful than culture. In a population studied by Roden et al., diabetics represented 36% of published mucormycosis cases. Among this diabetic population, 43% presented with rhinocerebral involvement and 16% presented with pulmonary involvement. Mortality among all patients was 76% in patients with pulmonary infection. Due to the high mortality, treatment must be initiated as soon as the diagnosis is suspected rather than waiting for definitive diagnosis.

Surgical debridement should be considered but is not always feasible, especially when necrotic tissue abuts important anatomic structures, as was the case in our patient.First line treatment is amphotericin B lipid complex at a daily dose of > 5 mg/kg or liposomal amphotericin B at a daily dose of > 3 mg/ kg. Patients with impaired renal function, those who fail treatment with amphotericin or develop major adverse effects should be treated with posaconazole 200 mg four times per day. Isavuconazole is a second-generation triazole that has shown promise in treating invasive pulmonary aspergillosis and mucormycosis and may have a more favorable side effect profile than current first-line drugs. Aggressive surgical resection should be considered in patients who do not show clinical improvement within 48–72 hours of starting appropriate medical therapy. Wedge resection may be considered if disease is limited but a lobectomy is often required and pneumonectomy may be necessary for extensive disease. A review of 87 cases of localized pulmonary mucormycosis without evidence of dissemination showed a 44% overall survival rate with a mortality rate of 55% in patients receiving medical therapy alone versus a mortality rate of 27% in patients who underwent surgery, most of whom also received antifungal therapy. These results may be biased by the fact that patients who have extensive, multilobar disease at the time of diagnosis may not be deemed surgical candidates due to the widespread nature of their infection, as was the case with our patient. Numerous previous case reports have described cases of invasive pulmonary fungal infection associated with marijuana smoking in immunocompromised patients.Most of these patients had hematologic malignancies, a well-known risk factor for invasive fungal disease. Our patient had no known malignancy. However, we suspect that the combination of poorly controlled diabetes and years of cigarette smoking leading to emphysema and increased susceptibility to pulmonary infection put him at increased risk of invasive fungal disease. We hypothesize that he inhaled airborne spores while smoking marijuana, leading to overwhelming pulmonary infection. Unfortunately, we were unable to perform microbiologic testing of the suspect marijuana due to the delayed presentation after onset of symptoms. Patients seeking pain relief by smoking marijuana may have conditions putting them at risk for opportunistic infections. In Canada and the Netherlands, where medical marijuana is dispensed under the regulation of the federal government, gamma-irradiation is used to sterilize medical marijuana before it is distributed to patients.

This practice is not yet commonplace in the United States, where rules and regulations vary state to state.Until sterilization of medical marijuana becomes routine in the United States, physicians should counsel immunocompromised patients, including those with poorly controlled diabetes, that smoking medical marijuana puts them at risk for overwhelming pulmonary infection due to invasive fungi.Tobacco use is the leading cause of preventable morbidity and mortality in the US.Cannabis  is the most prevalent and increasingly used illicit drug in the United States.Accumulating evidence consistently demonstrates that heavy or habitual marijuana use is associated with numerous short- and long-term deleterious health consequences,including but not limited to addiction,altered brain structure and connectivity,impaired memory and neuropsychological decline,psychosis,poor educational attainment,symptoms of chronic bronchitis,impaired motor coordination and traffic collisions,and diminished life satisfaction.Marijuana and tobacco use share potential common environmental influences,common mode of use,and are frequently used together. One study suggested that, during a lifetime period, 57.9% of those who ever used tobacco reported ever using marijuana and 90% of those who ever used marijuana reported ever using tobacco.Another study showed that, during the past month, the prevalence of marijuana use was 17.8% among past-month tobacco users and the prevalence of tobacco use was 69.6% among past-month marijuana users.Across the lifespan, either concurrently or at different times, prior use of either tobacco or marijuana substantially elevates the risk of subsequent initiation of the other and is associated with the progression to tobacco and marijuana dependence.Heightened susceptibility has been linked to genetic predispositions and putative neurobiological mechanisms that may facilitate increased urge and intensity of using each substance,promote progression to other types of illicit drugs,and precipitate relapse or hamper the success of quitting use of either substance.

Self-rated health  is a brief, validated proxy measure of overall health status.Among a variety of populations, SRH is strongly predictive of future morbidity and mortality, even after extensive adjustment for many covariates such as illness, depression status, functional and cognitive decline, and health care utilization.Although SRH is generated through a subjective, contextual, and non-arbitrary process, research shows that individuals with “poor” SRH have a two-fold higher mortality risk than that of those with “excellent” SRH.SRH has been adopted as a chronic disease indicator for overarching conditions and as a Foundation Health Measure for the Healthy People 2020 objectives that monitor progress toward promoting health, preventing disease and disability, eliminating disparities, and improving quality of life.Although epidemiologic studies have evaluated effects of marijuana and tobacco use on many health outcomes, combined patterns of marijuana and tobacco use and their impact on overall health are uncertain. To our knowledge, no study has assessed regular marijuana smoking, with and without current tobacco use, in relation to suboptimal SRH among US adult ever users of marijuana. Ever users of marijuana are an important population of concern. Given that habitual marijuana use may affect health outcomes, and that tobacco use is a serious public health problem,such a study may provide observational evidence to inform prevention efforts. Therefore, we sought to examine patterns of regular marijuana smoking and current tobacco use and their associations with suboptimal SRH among a nationally representative household-based survey sample of US adult ever users of indoor cannabis grow system by analyzing data from the 2009– 2012 National Health and Nutrition Examination Survey .We estimated the crude prevalence for the four mutually exclusive groups of regular marijuana use and current tobacco use, both overall and among age subgroups. We also calculated the age-adjusted prevalence by the direct method to the year 2000 Census population for these patterns among participants and subgroups stratified by sex, race or ethnicity, education, marital status, alcohol use, physical activity, BMI, health care access, and a history of cardiovascular diseases, diabetes, arthritis, and cancer.We produced unadjusted and adjusted prevalence ratios with multivariable generalized linear models for survey data.We used the variable for patterns of regular marijuana smoking and current tobacco use as the predictor and suboptimal SRH as the outcome while adjusting for sociodemographic, behavioral, and health-related risk factors.

To obtain additional information on current regular marijuana smoking, we estimated the prevalence for reporting suboptimal SRH by status of previous 30-day and 60-day regular marijuana smoking among regular marijuana smokers with and without current tobacco use.To estimate relative excess risk due to interaction  between current tobacco use and regular marijuana smoking,additional analyses were performed by using current tobacco use and regular marijuana smoking as two independent variables with their interaction term in regression models. Weighted analyses were performed to account for the complex sampling design to provide nationally representative estimates.Consistent with previous studies, our results show that approximately 40% of ever users of marijuana were currently using tobacco. Our findings further indicate that, when compared to non-regular marijuana smoking without current tobacco use, regular marijuana smoking without current tobacco use was significantly associated with a 34% increased prevalence ratio of reporting suboptimal SRH. A greater prevalence ratio was observed for current tobacco use and regular marijuana smoking,as well as current tobacco use and non-regular marijuana smoking.Results from previous research on effects of marijuana use are inconclusive. One study reported an improvement in capacity for recall of information was associated with cessation of marijuana use.Other studies showed persistent marijuana use was associated with long-lasting cognitive impairment, and that cessation of marijuana use does not fully restore neuropsychological functioning, especially among those marijuana users of adolescentonset.Another study found that marijuana use for up to 20 years was associated with periodontal disease but not with other physical health measures in early midlife.In this study, we did not detect any appreciable difference in reporting suboptimal SRH among regular marijuana smokers with and without current tobacco stratified by status of their past 30- or 60-day regular marijuana smoking. Moreover, the results from this and previous studies show that many unhealthy lifestyle health behaviors  are interrelated. Such behaviors frequently co-occur and are often associated with worse health outcomes.The findings of our study have a number of important public health implications. First, SRH is included in the public health key metrics such as Healthy People 2020 and CDC Healthy Day for guiding disease prevention and health promotion and for measuring health-related quality of life in the US population.Second, reducing tobacco use and initiation among youth and adults is an important public health goal.

Moreover, small sample sizes of students in different academic disciplines precluded meaningful analyses to understand whether or not the observed results held true for students pursuing different types of careers. Future research that replicates the results of this study are needed, particularly in light of the small, yet significant, effect sizes observed. While the associations between graduate degree completion and both alcohol use frequency before enrollment  and marijuana use frequency after enrollment  were statistically significant, the magnitude of these effects calls into question the practical significance of these findings. As discussed, prior research among other student samples supports these findings. However, this study alone should not be used as sole evidence of the presence of an association between substance use and graduate degree completion, and results should be interpreted with caution. This study contributes to the literature on the relationship between marijuana use and academic achievement.For graduate students who appear to be struggling academically, a comprehensive assessment that includes marijuana use might be warranted in order to understand possible risk factors for dropout. University communities have a unique structure and set of resources,and graduate school is an opportune time to intervene while these supports are in place. A multitude of factors influence graduate degree obtainment other than alcohol and marijuana use, and future research is needed to provide a fuller understanding of the barriers and facilitators of success during graduate school. Of particular value would be multi-campus studies that capture graduate student populations from a wide range of degree types and academic disciplines.

Recent data from the 2018 Monitoring the Future Study suggests there has been a resurgence of marijuana  use in young adults over the last three and a half decades.Specifically, vertical grow system past 12-month and past 30-day MJ use in 19–22 year old college students are at the highest levels reported since 1983. Furthermore, 43% of 19–22 year old college students report past year MJ use, 25% report past month MJ use, while about 5.8% report frequent MJ use.In an ongoing study examining the behaviors, attitudes and values of substance users, MJ was considered the least risky among illicit substances in 18–30 year olds.In addition, the study indicates that over the past 11 years, there has been a continuous decline in perceived risk of regular MJ use. Changing attitudes have likely contributed to the legalization of recreational MJ use in eleven states and Washington D.C. MJ use has also increased in states where recreational use has been legalized making it a critical time to better understand whether young adult MJ use affects neurocognitive functioning.Adolescence and young adulthood are periods of active biopsychosocial development and brain maturation. Given the protracted development of the prefrontal cortex, young adulthood is a critical period for the maturation of executive functions. Therefore, the establishment and maturation of structural and functional connections between the prefrontal cortex and other brain regions important in higher-order cognitive functions  during the third decade of life may be especially sensitive to the neurotoxic effects of substance use.The primary psychoactive constituent of MJ, delta-9-tetrahydocannabinol,directly targets endocannabinoid receptors located in the prefrontal cortex. Acute THC binding to cannabinoid receptor 1 has been shown to increase dopamine release and neural activity.THC exposure may disrupt cortical gamma oscillatory activity due to GABAergic reduction and neuronal hyperactivation in the prefrontal cortex  leading to disruptions in dopamine regulation which may contribute to cognitive impairments in executive functioning associated with MJ use.Previous studies have reported cognitive functioning impairments in adolescent and young adult MJ users.

Frequent MJ use has been shown to impair attention and concentration  as well as verbal fluency.On executive functioning tasks, MJ users were slower on Go trials on the Go/NoGo Task,made more commission and omission errors on the Stroop Color Word Test,and made more perseverative errors  and had lower executive function standard scores on the Wisconsin Card Sorting Test,compared to healthy controls. In addition, daily MJ use has been linked to executive functioning impairments in cognitive flexibility and inhibition,both of which play important roles in decision-making.Adaptive decision-making is necessary for selecting healthy choices without significant personal risk, but poor decision-making can lead to risky choice, such as the maintenance of heavy or frequent substance use. Previous research on decision-making in MJ users has been mixed. Many studies have indicated that frequent MJ use is associated with deficits in decision-making performance,while some studies have found no clear group differences between chronic MJ users and healthy controls.These mixed findings may be attributed to the heterogeneity of decision making tasks, variability in MJ use history and the neuro developmental stage at first MJ use. In addition, the ages of participants in these studies ranged from adolescents to middle-aged adults and the criteria for frequent MJ use varied from >1 occasion of MJ use/week in the past year  to 25 out of 30 days of MJ use for at least five years,highlighting differences in inclusionary criteria for MJ users.One of the most widely used neurocognitive measures of risky decision-making is the Iowa Gambling Task,which simulates real life decision-making, the cognitive ability to select the most adaptive course of action among a set of possibilities. Evidence of deliberate risk taking and impulsivity have been measured using IGT performance.Many studies examining the effects of chronic MJ use on cognitive functioning have utilized the IGT to measure decision-making performance. A study examining group differences on net IGT scores between healthy controls and MJ users who smoked MJ for at least two years and who currently smoked at least four times/week, showed that greater frequency of MJ use was related to poorer IGT performance.

This study found that cannabis users had significant impairments in decision-making and risk-taking compared to healthy controls,suggesting chronic MJ users have difficulty in changing their decision-making strategy towards advantageous card choices. In a subsequent study, frequent MJ users showed a preference for selecting decks having greater wins and infrequent, but greater punishments,further indicating that MJ users may have a more difficult time in anticipating and strategizing monetary gain and loss. Frequent MJ use has also been shown to influence brain activity in regions associated with decision-making while participants performed the IGT during functional magnetic resonance imaging  and positron emission tomography. A previous study indicated that chronic MJ users exhibited significantly less activity in the anterior cingulate cortex and medial frontal cortex, brain regions that are believed to play roles in impulse control and decision-making, during strategy development for the IGT.This reduction of brain activity during monetary loss suggests MJ users may be less sensitive to negative feedback. Furthermore, chronic MJ users showed increased regional cerebral blood flow in the ventromedial prefrontal cortex compared to healthy controls during monetary decision-making and reward processing which may indicate that MJ users have greater sensitivity to rewards.These studies provide support for the important role of the prefrontal cortex in decision making skills and highlight the vulnerability of this region to the effects of frequent MJ use during young adulthood.Despite growing research on the effects of frequent MJ use on cognitive deficits in memory, attention and psychomotor function,there has been less attention on the influence of frequent MJ use on executive functioning, especially in young adults.Specifically, the effects of frequent MJ use on decision-making performance is mixed and not well understood. While some studies indicate cannabis users have significantly impaired decision-making capacities and greater risk taking tendencies,other studies suggest no clear differences between frequent MJ users and healthy controls.To our knowledge, only one study  examined the effects of MJ use on risky decision-making within a narrow age range of 18–20 year old young adult college students and found MJ users showed a preference for selecting cards in decks A and B, leading to greater wins with infrequent but greater punishments.The current study aims to replicate and extend these findings by investigating the effects of frequent MJ use on risky decision-making in young adult college students, 18–22 years old.

We chose to specifically examine the effects of frequent MJ use on decision-making in this population as  MJ use is most prevalent during emerging adulthood,  the prefrontal cortex continues to mature during this time, and  MJ use has been associated with poorer academic outcomes in college students,suggesting a window of vulnerability to the effects of frequent MJ use on adaptive decision-making in this population. Furthermore, given that the prefrontal cortex undergoes sex-specific maturation during adolescence,examining the role of sex on decision-making may highlight important differences in risk-taking between MJ users and healthy controls. Specifically, research suggests female participants are more sensitive to losses in advantageous decks on the IGT compared to male participants and, as a consequence, need additional trials before they achieve a similar level of performance.These behavioral differences could be related to underlying neurobiological differences in the activation of the prefrontal cortex. Male participants may be better at suppressing reward-driven behaviors as right dorsolateral prefrontal cortex activity has been reported in males but not females during the IGT.Decision-making differences could also be associated with sex differences in the rate of white matter maturation, as male youth show steeper increases in white matter development relative to female youth.A previous study examined sex differences in decision-making on the IGT in young adult MJ users and found that heavier MJ use was associated with poorer decision-making performance in males but not females.However,mobile grow systems to our knowledge, no studies have examined group-by-sex interactions on risky decision-making in young adult MJ users and healthy controls.The aims of the proposed study were to examine the influence of frequent MJ use on risky decision-making in college students using the IGT. A secondary aim was to conduct an exploratory analysis examining group-by-sex interactions on risky decision-making in young adult college students. Since we were interested in examining decision making within active MJ users who were not yet undergoing cannabis withdrawal, we asked participants to remain abstinent from all substance use for 12 h prior to the study visit to attempt to avoid any withdrawal symptoms that may contribute to impairments in decision making. We hypothesized that  frequent MJ users would have poorer performance than healthy controls, indicated by lower net IGT scores;  frequent MJ users would show faster reaction times in card selection compared with healthy controls, which would reflect greater impulsive tendencies during decision-making; and  younger age at first MJ use, greater cumulative MJ use and greater recent MJ use would be related to lower net IGT scores in MJ users.

Participants were recruited through flyers posted around the community and at MJ dispensaries as well as through social media advertising. Written consent was obtained from participants who contacted the laboratory to complete an interview to determine eligibility for the study. Following an eligibility interview, eligible participants were invited to take part in a study visit that included measures of substance use and psychosocial functioning as well as neurocognitive tasks of executive functioning. All participants were asked to abstain from substance use for at least 12 h prior to the study visit to limit effects of acute intoxication on neurocognitive measures. No participants appeared intoxicated at the time of the study visit. After providing consent for participating in the study visit, participants provided a urine sample for a 12-panel urine toxicology test and completed a breathalyzer test to confirm absence of alcohol intoxication. All MJ+ had a positive urine toxicology screen for THC, while all HC had a negative urine toxicology screen for THC. Further, all participants had a blood alcohol concentration of 0.00 at the time of the study visit. A nicotine metabolite test for cotinine was not conducted for this study; thus, recent nicotine use was assessed through self-report. At the end of the study visit, participants were compensated with an Amazon e-gift card. All study procedures were approved by the Oregon State University Institutional Review Board  and were in accordance with ethical guidelines of research with human participants.The IGT was administered to participants on a computer. Four card decks  were displayed to participants on the computer screen. Participants were read a standardized task script and told that the objective of the game was to win as much money as possible.

Activation of cannabinoid receptors has been shown to enhance dopamine,which may be another pathway by which marijuana affects sexual function. Cannabinoid receptors have also been localized to other areas of the brain that control sexual function, including the hypothalamus, prefrontal cortex, amygdala, and hippocampus.Serum levels of endocannabinoids have been correlated with both subjective and objective measures of arousal.6 The strength and weakness of this study is that it is a single center study, which allows consistency of patient recruitment but does not allow for assessment of generalizability. It relied on women’s memory and perceptions of the sexual experience; however, it is real life, and all questionnaires rely on recall. It did not address the context of the relationship, co-use with other drugs, or the timing and quantity of marijuana use before sex, all of which contribute to the memory of the sexual experience. It does not specifically ask whether the marijuana was taken because the patient had the perception that it would enhance performance, which would be an inherent bias. This may be less likely because women who were frequent users  had the same positive relationship with improvement in satisfying orgasm. A further study could address the specific timing of marijuana use on the sexual domains though this would be difficult unless patients were enrolled in a study that required certain timing .Marijuana use dates back to 2727 BC to Chinese Emperor Shen Nung. After spreading through the Greek and Roman empires and into the Islamic empire of North Africa and the Middle East, it was brought to the Western hemisphere by the Spanish.

Originally lauded for its utility as fiber, it was not until its migration into North America that it began to be used in a similar fashion as it is today. Used in the form of hemp, it was seen throughout society as rope, clothing and even paper. While marijuana has been used by Americans recreationally for years, it is a subject that is becoming more commonplace in our modern society. According to the National Institutes of Health, marijuana use in 2015e2016 rose from 4.1% to 9.5% of the U.S. adult population. With more states eliminating the legal ramifications of its use and a growing debate about its federal legality, this is a subject that routinely makes local and national headlines. With a diverse array of commercial products becoming available from chocolate squares to oral sprays, cannabis grow racks is also no longer restricted to a rolled cigarette. The medical community has also joined the debate. The most obvious correlation between medicine and marijuana is medicinal marijuana. Marijuana’s effects have been well documented, allowing the push for its use as medicine within multiple specialities. Proponents of its use point to its effects on the endocannabinoid system. Studies show that through its impact on different pathways it may be used as an analgesic, immunosuppressant, muscle relaxant, anti-inflammatory agent, appetite modulator, antidepressant, antiemetic, bronchodilator, neuroleptic, antineoplastic and antiallergen.Medical marijuana also differs in chemical composition, containing a higher tetrahydrocannabinol  concentration and less cannabinol than the recreational version. This is even before taking into consideration the various extraneous agents that may be found within the available recreational drug.There is however, very little, if any research evaluating marijuana’s use in surgery. This paucity of literature presents a problem. While many surgeons may ask about recreation drug use including marijuana, many other drugs have established evidence based outcomes that allow variation in surgical planning as needed.

However, when it comes to marijuana, surgeons are left to determine what to do with this information on their own.Despite the multiple studies on the physiologic effects of marijuana use, clinical studies, if any, are not cited in the medical literature. This study reviews the literature available on marijuana’s effects and discusses potential complications that may result within the surgical setting. With a reported estimation of 10%e20% of patients between the ages of 18 and 25 years regularly using marijuana, this review seeks to become an initial step for further exploration of the subject and to reveal why there is a need for more in-depth research.A search on the effects of marijuana, marijuana and elective surgery, and marijuana’s effects on surgery was undertaken in PubMed, Medline, EMBASE, Google.com and Scholar.google.com. Articles were reviewed using the keywords “marijuana,” “elective surgery,” “surgery,” “anesthesia,” “complication,” “THC,” “tobacco” and “cannabis.” After removing duplicates, 263 studies resulted. After articles were identified, attention was paid to study design, type, outcomes and publication. The authors independently reviewed titles and abstracts to ascertain relevance to the topic at hand. Authors also searched reference lists of included studies as well as other narrative reviews.Due to limited research and reviews on this subject, information was utilized from articles on surgery in various fields, such as orthopedic, dental and bariatric with anesthesia considerations and general topics related to marijuana also examined. The following information was gathered: marijuana’s prevalence in the United States, marijuana’s effects on the cardiovascular system and pulmonary system, potential coagulopathies, marijuana’s effects in relation to anesthesiology, evidence based screening methods for recreational drug use, potential surgical complications that may result from marijuana use, and recommendations on marijuana use and surgery.When marijuana is smoked, THC and other cannabinoids are absorbed rapidly through the lungs with effects peaking in 15 minutes.

These effects can persist for up to a dose-dependent 4 hours in the acute setting. When ingested orally however, onset of effects is slower  but has a longer duration of action,due to continued absorption in the gut. This is despite a lower bioavailability due to first-pass metabolism by the liver which results in a blood concentration 25% of what is obtained if smoked. The cognitive/psychomotor effects can be present for up to 24 hours regardless of administration route. Cannabinoids are highly lipid soluble. This leads to a slow release into the bloodstream with a single dose not fully eliminated for up to 30 days. The cardiovascular effects of marijuana use range from benign to worrisome based on the timeline of use and dosage. In a series single blind study comparing the effects of high and low doses of THC in healthy young men, tachycardia was induced beginning within the time of inhalation, and persisting at least 90 minutes, with the maximum heart rate reached at an average of 30 minutes. The study also found a significant elevation in systolic and diastolic blood pressures as well as the presence of premature ventricular contractions in subjects who received the higher doses. These experiments showed a correlation between the dose and the tachycardic and cardiovascular changes. In addition, Malit et al.’s study on the effects of intravenous THC found the majority of patients to exceed the 100 beats per minute mark but also experience intermittent spikes in heart rate with a possible etiology of psychological distress. Beacons field et al. postulated a mechanism of beta adrenergic stimulation for the tachycardia as he was able to block the tachycardia with the use of propranolol.Pharmacology lays credence to this. At lower or moderate doses, marijuana increases sympathetic activity reducing parasympathetics and producing an elevation in heart rate, cardiac output and blood pressure. However, the opposite is true as the dosage increases.

At high doses, the parasympathetic system takes over, leading to bradycardia and hypotension with animal studies postulating that the sympathetic inhibition occurs due to the bio-active constituent of cannabis’s effects on the CB1 receptors. In addition to sinus tachycardia, marijuana use has been linked to multiple electrocardiogram  changes in various case reports. Daccarrett et al. found Brugadalike changes in a 19 year old male with a known history of cannabis use and no anatomical/functional abnormalities. A case was also reported in which cannabis use was linked to the development of atrial flutter and atrial fibrillation, while other studies have reported the presence of sinus bradycardia and AV block.Marijuana use also has a role as a risk factor for myocardial infarction. Aronow et al., found that while comparing marijuana to placebo, cannabis causes an increase in carboxyhemoglobin, a resultant increase in myocardial oxygen demand, decrease in oxygen supply as well as an induction of platelet aggregation. One case report showed a 21 year old male who presented with a ST elevation myocardial infarction due to plaque rupture as a complication of marijuana use. In Mittleman et al.’s analysis of over 3,800 cases of myocardial infarction, 124 patients reported use within the last year of which 37 reported use within 24 hours, with 9 reporting use within an hour of the event. The study found a statistically significant 4.8 fold increase in myocardial infarction within the first hour of marijuana use.In fact, as THC content of marijuana increases, there are a growing number of clinical studies demonstrating the association between cannabis use and adverse cardiovascular events. One such study followed 1913 adults prospectively and demonstrated that in patients with prior myocardial infarction, marijuana use up to once per week increased risk of death 2.5 fold while more frequent use yielded a fourfold risk of dying. Marijuana has also been reported as a risk factor for stroke. Over 80 cases have been reported in which patients had strokes, with a higher prevalence of ischemic strokes, that were associated with either a recent increase, in the days leading up to the event, or chronic history of heavy marijuana use.

They believed that the marked swings in blood pressure or the reversible cerebral vasoconstriction that resulted from cannabis grow system use were likely mechanisms of stroke but admitted that no firm conclusions could be drawn without further studies.In addition, Lawson reported a similar belief that drug induced vasospasm was a plausible explanation for TIAs, but also with the caveat that due to the confounding medications/illicit substances being used in his patient, no direct association could be determined. Also of interest is marijuana use’s effect on other cardiovascular vessels. When cohort studies were performed comparing marijuana users with resultant limb arteritis to patients suffering from thromboangiitis obliterans, marijuana associated arteritis occurred in younger, usually male patients with a unilateral, lower limb as the common presentation. The most common route of marijuana administration is inhalation via smoking. Due to the unfiltered nature of the marijuana cigarette compared to commercially available tobacco cigarettes, the amount of carcinogens and irritants, like tar, that enter the upper airway is increased with approximately a three-fold increase in tar inhalation and one third more tar deposition in the respiratory tract. More specifically, the tar produced from cannabis smoke contains greater concentration of benzanthracenes and benzopyrenes  than tobacco smoke. In addition, as compared to smoking tobacco, there is a two-thirds greater puff volume, one-third greater depth of inhalation and a four-fold longer breath-holding time, all of which are common practices to try to maximize THC absorption, which is around 50% of cigarette content. These practices result in five times the amount of carboxyhemoglobin levels as compared to the typical tobacco smoker despite the presence of similar quantities of carbon monoxide from the incomplete combustion of the organic compounds found within each product. In reporting his case, Schwartz theorized that high temperatures in which marijuana burns compared to tobacco may increase the irritancy of marijuana to the mucous membranes. While the higher temperature is a possibility, the evidence of marijuana’s irritancy is well documented. In a cohort study comprised of 40 healthy patients, Roth et al. showed that cannabis smokers had significantly increased visual bronchitis index scores resulting from large airway epithelial damage, edema, and erythema. On mucosal biopsy, goblet cell hyperplasia with subsequent increase in secretions, loss of ciliated epithelium and squamous metaplasia were also present in 97% of smokers. They concluded that marijuana use is associated with airway inflammation that is similar to that of a tobacco smoker. A cross-sectional study on over 6000 patients, from 1988 to 1994, found an increased incidence of chronic bronchitis symptoms such as wheezing and productive cough occurring in patients 10 years younger, on average, than tobacco smokers. Case-control trials performed found similar findings with regards to increases in wheezing, shortness of breath, cough and phlegm as well as the similarities with tobacco use.

The changes in treatment rates are also displayed in Figure 4. Regression models suggest a significantly declining treatment rate only for the Netherlands , Finland , and Slovenia . In ten countries, treatment rates significantly increased. Modest increases were recorded in Greece, Poland, Austria, Slovakia, and Portugal , while more pronounced increases were present in Romania, Belgium, France, Malta, and Sweden . Based on those 17 countries providing continuous data between 2010 and 2019, the upward slope in treatment rates had come to a halt in the year 2015 and has mostly plateaued since then . The available data on TDI coverage suggests a high degree of variation between countries and over time, including a declining number of treatment units from which data were collected since 2014 .Public health monitoring indicates that cannabis use is prevalent in Europe. Although estimates should be interpreted with caution due to potential error, the best available data at present indicates that an estimated 3¢9% of all adults aged 15 to 64 reporting past month use. There is a considerable variation in prevalence of use, ranging from 9¢1% in Spain to less than 1% in Malta, Hungary, and Turkey. Approximately 1 in 7 past-month users were estimated to meet CUD criteria, with substantial heterogeneity between countries. In countries where cannabis use is more common, such as in the Netherlands and Spain, the share of users meeting CUD criteria appears to be lower than in countries where cannabis use is less common, such as Malta and Hungary.

However, there are also exceptions to this, such as the UK, which has both relatively high rates of cannabis use and of CUD. At the European level, the bulk of trend data converge on showing that cannabis use and related problems have increased in the past decade. The available data indicates that rises in prevalence rates were reported in all age groups. Among adults aged 35 to 64 years, trimming tray with screen prevalence of past month use increased by 50% or more. These findings are similar to reports from European student surveys and recent trends in the USA, where the largest increases in prevalence of use have occurred in middle-aged adults. Consistent with rising prevalence of any use and high-risk use patterns, treatment rates have also risen in many countries, reaching a plateau in 2014. The high level of treatment rates for cannabis creates problems for healthcare providers. Psychosocial interventions such as Motivational Interviewing and Cognitive Behavioural Therapy have been shown to be effective at reducing cannabis use. However, there is a lack of approved pharmacotherapies for the treatment of cannabis use disorders, and limited effectiveness of psychosocial interventions for people with comorbid mental health problems such as psychosis. Lastly, stark and modest increases in cannabis potency levels have been registered for resin and herbal cannabis, respectively, corroborating previous analyses in Europe and internationally. In contrast to these trends, CUD prevalence is estimated to have declined in the past decade in most countries. These findings are consistent with survey data from the United States, showing that while the prevalence of cannabis use increased from 2001-2002 to 2012- 2013, the prevalence of cannabis use disorders in cannabis users decreased. However, potency level may be implicated with other health outcomes than CUD, such as psychotic outcomes or genotoxic and epigenotoxic effects.This indicator is based on general population surveys, which have the usual problems of substance use surveys in the last decade: nonrepresentative sampling frame excluding key risk groups, high degree of non-response and use of self-report. Moreover, the validity of prevalence estimates may vary between countries, which could increase risk of bias when comparing estimates across different countries.

Undercoverage is not as easily quantified as for legal substances such as alcohol, as objective indicators such as sales data or wastewater analyses do not routinely exist or are hard to interpret in comparison to the standard indicators. Further, the lack of uncertainty measures prohibited to apply robust statistical methods to study trends in cannabis consumption. Lastly, we do not have any information on the purpose of consumption but assume that only a minor fraction of users do take cannabis for medical purposes . For future monitoring, survey data should distinguish between medical and recreational cannabis users. Despite these limitations, survey-based cannabis use prevalence constitutes one of the best indicators available for public health monitoring purposes. In the 2021 European Drug Report, the EMCDDA focuses on cannabis use among young adults. While we also found indications for increasing use in this age groups, our findings add that cannabis consumption has apparently become more common among 35 to 64 year-olds. Albeit absolute use levels remain lower in this age group, this is a trend worth noting. This trend could be driven by an aging population of users or by the increase in medical use of cannabis. Prescription data from Germany show that patients using cannabis flowers on prescription are on average 46 years old. Another possibility, supported by data from the USA, is that the proportion of older adults who disapprove of cannabis use may have decreased over time. While the underlying reasons for an aging population of cannabis users are yet to be singled out, the prolonged use of cannabis might be associated with an increase in the risk of lung cancer or chronic obstructive pulmonary disease both of which are rather rare among younger adults.

Moreover, acute cannabis use is a risk factor for traffic collisions and this affects all ages regardless of the purpose of use. Thus, if the aging and growing population of cannabis users are driving under the influence of cannabis, this could increase the number of motor vehicle accidents in Europe. Our findings further suggest an increase in daily cannabis use prevalence. While similar trends have been reported for the USA, such patterns have not been reported for Europe so far. Further research should examine whether prevalence of risky use patterns increased over and above prevalence of any use or in other words: have use patterns among current users become riskier?In contrast to all other trends, the prevalence of CUD did not show indications of increases in Europe. As the CUD data constitute smoothed estimates obtained from statistical models, there are some problems inherent to these data, such as not appropriately representing the true fluctuation in the data. However, as CUD prevalence is estimated from cannabis use prevalence, the diverging trends question the validity of the CUD estimates. The consistency of select GBD estimates have been questioned in previous studies and our results add that estimation procedures for CUD prevalence may be revisited and improved. An additional consideration is that the validity of CUD estimates may vary between countries, which limits comparability of estimates across countries. Given the outlined limitations associated with available TDI and CUD data, there is a need to improve indicators for high-risk cannabis use or experience of cannabis-related problems in Europe. We propose to use high-frequency use patterns, such as daily use and the EMCDDA should provide these data by country, year, sex, and age on their website. In the long-run, however, an indicator for high-risk use considering more than just frequency of use should be established, ideally supplemented with data on quantity of use .Our analyses show that the number of treatment units contributing to the TDI varies greatly between countries and over time.

The large gaps in treatment rates far exceed the variation that would be expected based on prevalence of use and of CUD, questioning the validity of the estimates across time and space. Moreover, up-to-date information on TDI coverage, i.e., the share of all relevant treatment units covered in each country, is not available. Thus, we recommend that between-country comparisons should not be undertaken without accounting for methodological differences. Further, an increase in treatment rates can reflect a number of different factors , such as TDI reporting completeness or quality, a higher willingness of users to seek treatment, or increased availability of treatment. We recommend that, where feasible, improvements to TDI data quality should be made to facilitate understanding of true treatment demand and enable robust estimates of change.As such, they should not be assumed to be representative of the type of cannabis used at the retail level. Law enforcement methods create a risk of bias in selection according to various factors such as degree of criminal involvement, ethnicity, age, gender, and location. By contrast, cannabis potency data reported by the Netherlands can be assumed to be representative of cannabis available at the retail level, as data are collected using a standardised protocol consisting of random sampling from national retail outlets each year. We recommend that, where possible, additional European countries should sample cannabis from sources other than seizures in order to improve the reliability and validity of the data. As policies towards cannabis are becoming more permissive in Europe, this may facilitate improved monitoring of cannabis potency at the retail level. An additional consideration is that for all countries reporting data on cannabis potency, the reliability of data may be influenced by the sample size of cannabis products used to create summary estimates for each country and year, and the laboratory equipment and analytical protocol used to estimate potency. Information on these potentially confounding variables are not available at present. Finally, trimming tray for weed concentrations of cannabidiol are not monitored at present.

The public health relevance of cannabis potency indicators is evidenced by findings that THC concentration was associated with progression to the first symptom of CUD and greater severity of CUD, especially among younger people. High-potency cannabis was also associated with increased risk of psychosis, and with frequency of use, cannabis-related problems and anxiety. Our findings suggest greater THC concentrations in cannabis resin, which is produced by extracting material from the cannabis plant. The increase in potency of cannabis resin in Europe may be attributable to a shift towards THC-dominant cannabis plants in Morocco – the primary producer of cannabis resin for the European market. The increased THC concentrations in resin may translate into greater risk of harm for users preferring this type of cannabis. Possibly, the increased risk could be offset by dose titration or higher concentration of cannabidiol found in resin . However, as findings on the protective effects of cannabidiol have been inconsistent, it remains to be studied empirically whether resin use is associated with an increased risk. In light of the increased public health risks and the uncertainty in the underlying data, we see the need for improved monitoring of cannabis potency in Europe. The need for better data is further substantiated by changes in the cannabis market, such as the emergence of products containing high levels of cannabidiol in Europe and the widespread use of highly concentrated cannabis extracts in North America.Despite an extensive history of use as a medicinal plant spanning ancient cultures, cannabis use is contentious in many jurisdictions as it has been considered a social drug of abuse since the mid-1930s. Over the last two decades, meaningful legal, sociocultural and economic change has led to the establishment of medicinal cannabis research programs in several countries, which have validated the therapeutic use of cannabis for indications including: chronic neuropathic pain, certain intractable epilepsies, the vomiting and spasticity of multiple sclerosis, and chemotherapy-induced nausea. Further to this, the use of medicinal cannabis has expanded into paediatric and vulnerable patient groups and regulated markets for recreational use have developed in some jurisdictions. Accordingly, quality control across the supply chain is increasingly important to ensure that cannabis products are safe and have well-defined chemical and therapeutic profiles. Critically, the complex relationship between chemical profiles and therapeutic activity requires further exploration. Presently, the activities of the three most abundant neutral cannabinoids – Δ9 -THC, CBD, and CBG – have been studied closely, exhibiting properties including: analgesic, anticonvulsant, and anti-inflammatory. However, the full potential of medicinal cannabis may not be realised without leveraging the full diversity of cannabinoids. Over 140 cannabinoids have been identified, many of which have their own inherent pharmacological properties. This includes the acidic cannabinoids which have significant anticonvulsant activities, contrary to the historical perspective that they were inert precursors which only acquired activity after decarboxylating into the neutral cannabinoids.

As lung inflammation is a critical malfunction in case of COVID-19. Therefore, the reduction of lung inflammation has been tested in the mice animal model. Interestingly, cannabinoids isolates such as CBD and THC has also been tested in human as well even long before the onset of global pandemic owing to the spread of severe acute respiratory syndrome coronavirus type 2 infection . Immune responses during severe cases of COVID-19 trigger the inflammation of human lung tissue resulting in acute respiratory distress and failure. This immune response for the overproduction of the pro-inflammatory cytokines is known as a cytokine storm . Respiratory distress from the COVID-19 induced lung inflammation is the leading cause of high mortality rate. Phyto-cannabinoids especially CBD have exhibited a remarkable anti-inflammatory effect through CB2 inhibitory activity and agonistic effect on the peroxisome proliferator-activated receptor g reviewed in . Additionally, CBD, CBN, and THC have also been shown to exhibit anti-viral effect against COVID-19 in cell-based assay with the same potency as the standard clinical references. However, the complete antiviral mechanism of cannabinoids against SAR-CoV2 infection is still unknown. Therefore, detailed pharmacological research studies are urgently needed to explore the immunotherapy potential of cannabis against SARS-CoV2 infection.Cannabis legalization fueled the scientific research in cannabinoid compounds for potential in medicinal, pharmaceutical, and neurological applications. However, with recent developments in sequencing technologies, there has been a paradigm shift in cannabis research toward the genetical genomics of fiberand drug-type plants. Remarkable growth in genomic data combined with fast-paced development of artificial intelligence -based data analysis tools have made it possible to explore cannabis plant at the genetic and molecular levels. Integrated omics studies combining genomic and expression data with metabolite profiles are now beginning to understand the genetical regulation of the cannabinoid biosynthesis pathway.

Especially, by unraveling the association between the expression of cannabinoid genes with THC:CBD ratio and cannabinoid content. The knowledge could be further applied to genetically modify cannabis with optimized pathways for preferred metabolite yield and composition. Advanced biotechnology methods could be further extended for recombinant production of cannabinoids in metabolically engineered hosts such as yeasts or bacteria. Currently,grow tent hydroponic the recombinant production of THC in yeast is challenging owing to unstable THCA and CBGA expression and high amounts of side products. However, in the future, the combination of genetic technologies to obtain enhanced expression rates will lead to enhanced cannabinoid yields in an economically feasible manner. In addition, cannabinoids have been recently shown to exhibit anti-inflammatory and immunosuppressing effects against the COVID-19 immune response. However, further evidence-based clinical studies are needed to determine the efficacy and safe dosage of cannabis extracts for treatment or prevention of COVID-19. Pharmacological research coupled with rapidly evolving genome-based biotechnology will further facilitate exploring cannabis plants for tremendous potential in drug-discovery.Pain management remains a major challenge in orthopedics. Surgeons employ a multitude of strategies to combat this challenge, including multi-modal pain regimens and preoperative opioid counseling.A recent review of medical cannabis in orthopedic surgery proposed that MC may provide an additional pain management option for patients with chronic pain.Chronic pain, defined as pain that fails to respond to traditional pain control regimens and lasts greater than 3 to 6 months, is one of the most widely recognized indications for MC use and has been reported to be the primary indication for MC use in two-thirds of patients presenting to MC dispensaries in the northeast.MC use has become more widespread in recent years and is currently legal in 36 states and 4 United Sates territories.

This has been paralleled by a decreased perceived risk of cannabis use reported in a nationwide survey of United States citizens from 2002 to 2014.However, limited evidence exists on MC use in orthopedic surgery and on patient perspectives of this novel therapeutic. One descriptive qualitative study of spinal cord injury patients found that patients used MC when other pain management strategies failed and when they had both initiative and connections to educate themselves on MC use.Heng et al investigated musculoskeletal trauma patients’ opinions on MC and found that most patients thought it could be effective in treating musculoskeletal pain.However, there is an overall paucity of research on hand and upper-extremity patient perspectives on MC. This patient population may differ from other orthopedic conditions in that many present electively, it includes conditions with a mix of acute and chronic pain and includes patients of a wide age range. Many other orthopedic sub-specialties include a predominantly older population or see patients in the acute trauma setting. The purpose of this study was to evaluate hand and upperextremity patient perspectives of MC and its use in treating common hand and upper-extremity musculoskeletal conditions. We further sought to identify the prevalence of patients already using MC in this patient population, perceived barriers to MC use, and opinions on the legality of cannabis. We hypothesized that most patients would consider using MC for common orthopedic conditions, and that older patients would be more reluctant to use MC compared to younger patients.Institutional review board approval was obtained prior to initiation of this anonymous cross-sectional survey study. From October 2020 to January 2021, all patients who were at least 18 years old and presenting for an office visit at a metropolitan academic institution with clinic sites across New Jersey and Pennsylvania were asked to participate in this study.

All patients presented with a hand or upper-extremity complaint to 1 of 3 board certified, fellowship-trained orthopedic hand and upper-extremity surgeons. Medical cannabis is legal in both states where the survey was conducted, with New Jersey legalizing MC in 2010 and Pennsylvania in 2016. Patients completed a survey that was created by the study investigators regarding patient opinions of MC, including opinions of its legality, safety, costs, and potential barriers for use . Medical cannabis was defined in the survey as any publicly available legal MC product, which included topical, inhalational, and oral cannabis products. All survey responses were collected and stored electronically , with no identifying patient information collected as part of the survey. During the study period, 937 clinic patients were solicited to participate in the study.Statistical significance was set at P < .05.The present study identified numerous findings regarding hand surgery patient perspectives of MC. The majority of patients reporting to hand and upper-extremity orthopedic surgery outpatient offices would consider using MC for chronic pain control or for pain associated with many common orthopedic conditions. As MC use increases throughout the United States and as more MC research continues to emerge, it is important for surgeons to understand how patients perceive these substances and what factors may represent barriers to use. Most patients in our study reported that they would consider using MC for a variety of acute and chronic orthopedic pain conditions and believed it could effectively treat musculoskeletal pain. This is consistent with other orthopedic patient populations’ beliefs on the utility of MC. In a survey of orthopedic trauma patients, 81% believed cannabis can be used as a medication, and 78% believed it could be used to treat acute pain.9 In a study of elective surgery patients at a large academic center, inclusive of both orthopedic and nonorthopedic procedures, most patients believed MC could be at least somewhat effective for postoperative pain and chronic pain , and most patients would use MC if prescribed by a physician.

The positive patient response to MC as a potential pain control option brings into question the clinical effectiveness of MC in treating musculoskeletal pain. In multiple prior studies, cannabis users subjectively reported that cannabis provided effective pain relief.Of orthopedic trauma patients who used RC during recovery, 90% believed that it reduced their pain symptoms, and 81% believed it reduced the amount of opioids they required.Similarly, a survey of MC users, most being treated for chronic pain, revealed that 75% believed MC was effective in treating their pain and positively impacted their quality of life.Further, a study of orthopedic surgery patients found that preoperative RC users had lower pain scores and improved lower-extremity activity scores compared to non-cannabis users.Though most orthopedic surgery patients in the literature believe that MC is an effective treatment for pain, multiple review articles conclude that only low to moderate-quality evidence exists to support pain reduction with MC. These reviews also call for additional research on the safety, efficacy, and dosing of MC prior to making definitive conclusions on MC for pain management.To date, cannabis research has been limited by the federal classification of cannabis as a Schedule 1 substance, which has presented many barriers for researchers to perform high quality clinical trials.In our cohort, 74.7% of patients believed MC to be safe for treating orthopedic conditions and 74% of patients agreed or strongly agreed that MC was safer than prescription opioids for common pain conditions. While opioids are associated with many adverse outcomes including overdose and death, cannabis is likely perceived as safer as it is not associated with either of these critical major side effects.Despite this, other side effects of cannabis use must be considered. Cannabis use has been linked to negative mental health illnesses , impaired cognition, and increased rates of cardiovascular and cerebrovascular events. There is also a reported increased risk of motor vehicle collisions, including fatal accidents, in the acute setting following cannabis use.Negative consequences of cannabis use have also been described in total joint arthroplasty, although the evidence is inconsistent. One study reported no difference in short-term outcomes in primary total knee arthroplasty with cannabis use,grow tent for sale while another reported an increased risk of revision associated with cannabis use disorder.However, these studies are limited by the mixed inclusion of both MC and RC use.Lastly, the impact of cannabis use on anesthesia should be considered. A recent review of the perioperative care of cannabis users highlighted increased incidence of hyperreactive airway, intraoperative hypothermia, andcerebrovascular ischemic events. 

These studies are limited by the federal classification of cannabis as a Schedule 1 substance, and further studies are needed to better inform patients on the risks and benefits of MC. Interestingly, despite our cohort’s support for MC use as an alternative to opioids, only 26% believed MC could be used as a treatment for opioid use disorder. There is limited and contradictory evidence on the effects of cannabis on opioid use. One population level study found lower average opioid overdose mortality rates in states with legalized MC. Another study of orthopedic surgeons prescribing opioids to Medicare Part D patients found a decrease in opioid prescriptions in states with legal MC.Most studies on the impact of cannabis on opioid use in postoperative patients focus on the effect of preoperative RC use on perioperative and postoperative opioid requirements. Increased postoperative opioid requirements have been reported for orthopedic trauma patients. and total joint arthroplasty patients who were RC users.In contrast, other studies reported no difference in opioid requirements for RC users among total joint arthroplasty patients and elective surgery patients, inclusive of orthopedic and nonorthopedic procedures.None of these studies reported specifically on the effects of legal MC use on opioid requirements. One study of total hip arthroplasty and total knee arthroplasty patients treated after surgery with dronabinol, a synthetic prescription cannabinoid, in addition to a standard multi-modal pain regimen found a lower mean length of stay and lower averageopioid use.Further studies are required to elucidate the impact of multi-modal pain regimens inclusive of MC on opioid requirements in orthopedic surgery patients. Cost was reported by nearly 50% of our patients as a potential barrier for MC use, and over 70% reported the cost as either “expensive” or “not affordable.” A previous study of MC users also revealed the most common negative aspect of MC use was the associated cost, where patients reported spending over $2,000 per year on MC.The cost of MC varies by state and by specific product and is challenging to study, given the heterogeneity of the required quantity. A recent study by the Minnesota Department of Health found that the average 30-day cost per patient using MC to treat pain was $314 in 2019.35 Over 90% of patients in our cohort, greater than the number of patients that endorsed a willingness to use MC, supported insurance coverage for MC. Currently, no insurance companies cover MC.