Recognizing this, ACOG should assess whether the benefits outweigh the harms of screening in the context of high CPS reporting rates, and do more to change policies and practices that continue to threaten and punish pregnant people who use cannabis. Third, prenatal providers might benefit from medical education and ongoing training about current evidence on the health effects of cannabis use in pregnancy, the use of harm reduction strategies in addressing substance use, and patient-centered communication strategies that include referrals to mental health, community peer support, and other resources. Such strategies could better engage people who use cannabis in prenatal care, rather than contribute to them fearing judgment and punishment. This study has several limitations. First, since we recruited via online groups in California and through group classes, some participants may have been socially connected with each other, and therefore may have been influenced by each others’ views and experiences. Second, by design, all participants were California residents, and most were in the San Francisco Bay Area, a region with historically high rates of support for cannabis use and legalization . This may have reduced social desirability bias in interview responses, but could also have affected participants’ perceptions of cannabis use in pregnancy. Third, a high proportion of our sample used cannabis grow racks daily, which may not represent common patterns of use in pregnancy . While broad generalizability is never the aim of qualitative studies , the frequency of our participants’ cannabis use suggests limits on the populations to which these findings may be transferable . Finally, while we aimed to recruit a diverse sample, our study was not designed to examine whether experiences varied by demographics, nor did we explicitly ask people to reflect on how racism may have influenced experiences.

This is an important area for future research, as legal scholars note that CPS reporting for substance use in pregnancy is just one form of state policing of reproduction that is disproportionately imposed on pregnant people of color, especially Black women . The study also has strengths. First, our unique recruitment methodology yielded a diverse sample of participants from across socioeconomic and racial/ethnic groups. People of all racial/ethnic backgrounds and socioeconomic positions use cannabis, including pregnant people of all backgrounds . Yet many prior studies sample from a single private HMO system or are dominated by people of low income or a single racial/ethnic group . Our sample more accurately reflects the diverse demographics of people with the capacity for pregnancy who use cannabis in the U.S. . Second, interviewing over the phone allowed for anonymity and flexibility and may have increased participants’ comfort, which fostered rapport with participants and free expression of their views. Third, our experienced, responsive interviewer was able to engage participants in in-depth conversations, yielding abundant rich data on their multi-faceted views and experiences. Extraction is critical to analyzing plant constituents and assaying activity to aid in formulation development. Selecting extraction conditions is important as optimal conditions provide the desired plant bioactive compounds with minimal decomposition. Design of Experiment is an advanced, versatile tool for systematically testing production steps during research and development. DOE can be used across scientific fields for designing screens, comparing independent variables, identifying transfer functions, optimization, and robust design. This requires less time, is cheaper, and uses fewer chemicals than the traditional One Factor at a Time trialing. Additionally, it has been used to identify interaction effects and characterize surface responses. Eco-friendly, sustainable extraction techniques, such as pressurized liquid extraction, microwave-assisted extraction, ultrasound-assisted extraction, and supercritical fluid extraction , are gaining attention in research and development fields involving bioactive plant compounds.

SFE is particularly beneficial owing to the ability of supercritical fluids to penetrate solid matrices deeper and faster than other phases. This arises from the physical properties of a supercritical fluid, specifically, its density and viscosity, which are comparable to the liquid and gas phase, respectively, and the diffusivity, which is intermediate between gas and liquid. Importantly, SFE commonly employs carbon dioxide as the extraction solvent, which is suited for medical applications as it is inert, non-toxic, economical, easily accessible, and easily removed, and is already approved as a food-grade solvent. Extracts can be obtained via SFE at low temperatures and selectively isolate solvent-free products without byproducts. Additionally, the physicochemical properties of carbon dioxide at supercritical conditions favor the extraction of non-polar compounds. While the requirement for high-pressure makes this technique relatively expensive compared to conventional methods, its operational costs are economically acceptable, particularly for value-added products. Cannabis contains a number of medically valuable bioactive constituents, including cannabinoids and Δ9 -tetrahydrocannabinol and terpenes.Previous work reported the extraction of bioactive compounds from cannabis plants using SFE, which produced purer extracts than other techniques, such as maceration. Furthermore, SFE can separate other groups of compounds from cannabis for use in applications such as food additives, cosmetics, and aromatherapy. Cannabinoid-containing products are already used in medicine for a variety of conditions. For example, Sativex®, an oromucosal spray composed of approximately 2.5 mg CBD and 2.7 mg THC per 100 μL, has been developed for treating moderate to severe spasticity due to multiple sclerosis.

Epidiolex®, an oral solution composed of 100 mg/mL CBD, is used to treat seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. As cannabis extracts and cannabinoids are poorly water-soluble with high octanol/water partition coefficients, they are slowly absorbed via the gastrointestinal mucosa, resulting in low bioavailability when taken orally. Several techniques can enhance the solubility, dissolution, and bioavailability of poorly water-soluble drugs. Particle size reduction techniques, such as mechanical micronization or nanosization , and engineered particle size control can enhance drug solubility and dissolution. Drug bioavailability can be improved using self-emulsifying drug delivery systems , complexation with cyclodextrins, polymeric micelles, freeze-dried liposomes, and solid lipid nanoparticles. SEDDS, or self-emulsifying oil formulations, are lipid-based formulations that incorporate isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, and co-surfactants. Upon exposure to aqueous media , they undergo self-emulsification to form oil-in-water microemulsions or nanoemulsions with a droplet size ranging from 20 nm to 200 nm and are called self-microemulsifying drug delivery systems or self-nanoemulsifying drug delivery systems , respectively. The distinction between SMEDDS and SNEDDS varies in the literature, with SMEDDS reported to have droplet sizes ranging from less than 50 nm to less than 250 nm and SNEDDS defined as less than 100 nm. In contrast, SEDDS typically produce an emulsion with droplet sizes between 100 nm and 300 nm, although they have also been described as greater than 300 nm. SEDDS possess several advantages over conventional drug delivery systems: enhanced bioavailability, reduced local irritation of the gastrointestinal tract, physical and thermodynamic stability, and industrial scalability. SEDDS formulations typically incorporate P-glycoprotein inhibitors, as P-glycoprotein is known to decrease the oral bioavailability of several drugs. P-glycoprotein reduces absorption and oral bioavailability by increasing drug excretion from hepatocytes and renal tubules. Tween® 80, reported to be a P-glycoprotein inhibitor, is a primary surfactant in SEDDS formulation.

It permeabilizes the plasma membrane lipid bilayer by inserting into the lipid tails. It can also interact with the polar head of the plasma membrane and disrupt hydrogen and ionic bonds, which can help to inhibit P-glycoprotein activity. Seized cannabis is destined for destruction following adjudication. Rather than destroying seized cannabis, it could find use in research and development. This work took advantage of seized cannabis to optimize the SFE system using the Box-Behnken design. SEDDS were prepared from cannabis extract obtained under the optimal conditions to enhance dissolution. The formulation parameters were optimized using the 32 factorial design to minimize droplet size and emulsification time. The cannabis extract obtained from the optimized SFE system was dissolved in ethanol via ultrasonication for 1 h, winterized by freezing for 2 h, and vacuum filtered. Ethanol was removed from the extract by rotary evaporation . Pseudoternary phase diagrams of blank microemulsions, composed of a surfactant mixture of varying Tween® 80 and Span® 80 ratios , coconut oil, and water, were constructed using the water titration method. The three components were vortexed in a test tube for 30 s at ambient temperature. When a clear solution was obtained, water was gradually added with continued mixing. This step was repeated until the solution became turbid. SEDDS were prepared similarly to the blank microemulsions but without the addition of water. The ratios between the Smix  and coconut oil were based on the 32 factorial design . The winterized cannabis extract was added to all formulations and vortexed at ambient temperature for 1 min. Droplet size, size distribution, zeta potential, and emulsification time were determined for all formulations. Droplet size and emulsification time were analyzed by DesignExpert® version 11, providing mathematical models and their associated equations. Response surfaces were produced for all formulations. The optimal formulation resulted in the smallest droplet size and the shortest emulsification time and was used to assess the prediction accuracy, with the error reported. A dissolution test using the optimal SEDDS formulation was performed to confirm enhanced dissolution of the cannabis grow system extract. Pressure plays an important role in both the overall extraction yield and the quantity of bioactive compounds extracted. Increasing the pressure from 17 MPa to 34 MPa is reported to increase the yield of cannabis extract and its THC content. However, this work found that increasing the pressure increased the extraction yield but decreased the CBD and THC content. This supports the general principle that higher pressure increases solvent strength and decreases extraction selectivity, making the optimization of multiple extraction factors important to obtaining high extraction yields and selectivity.

Temperature significantly affected extraction yield but not CBD or THC content, which is consistent with previous reports. Ethanol has been used as a co-solvent to improve the solubility of polar compounds. Increasing the ethanol content was found to increase the extraction yield but decreased the CBD and THC content, similar to pressure. A previously optimized SFE system used 10 MPa, 35 ◦C, and 20% ethanol to maximize cannabinoid content. Another work varied pressure from 15 MPa to 33 MPa, temperature from 40 ◦C to 80 ◦C, and ethanol from 0% to 5% to maximize THC content. This work found that low pressures extracted more THC, temperature had no effect on THC content, and 2% ethanol gave the highest THC content. SFE has also been optimized for larger-scale cannabis extraction, with the optimal conditions determined to be 32 MPa with a carbon dioxide flow rate of 150 g/min over 600 min. This present work identified 18 MPa, 40 ◦C, and no ethanol as the optimal conditions. A possible explanation for the different conditions is the high concentration of cannabinol, an oxidized degradation product of THC, present in the seized cannabis used in this work, which could be associated with the aged cannabis raw material. Additionally, extracts were highly viscous when little ethanol was used. As the optimal conditions in this work did not include ethanol, the extract was extremely viscous, with some of the material remaining in the machine and negatively impacting the extraction yield. It is possible that the addition of minimal ethanol could increase extraction yield as well as cannabinoid content. This work developed SEDDS based on a microemulsion formulation. Microemulsions were prepared to select the suitable surfactant and oil. Single surfactants could not effectively microemulsify the natural oils and water.Particle sizes larger than 300 nm may not be absorbed by intestinal mucosa. Previous work found that small particles with a low magnitude negative charge and moderate hydrophilicity can easily pass through the small intestinal mucus layer. The SEDDS developed in this work were negatively charged with a droplet size of approximately 200 nm, suggesting that they could be absorbed following oral administration. The negative charge of SEDDS typically results from the freefatty acid molecules in the oil droplets. A 30 mV zeta potential is generally accepted as the threshold for the stability of colloidal systems. Zeta potentials above the threshold produce strong electric repulsion forces, increasing dispersion stability. The negative charge of the SEDDS developed here exceeded − 30 mV, indicating that it could promote stability and good dispersion of the system by preventing droplet aggregation upon contact with gastrointestinal fluid.