Journal of cannabis research最新文献

Background: Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic phytocannabinoids that have significant, broad-spectrum therapeutic potential in a variety of pharmacological areas, but their unfavorable pharmacokinetics, such as extensive first-pass metabolism and low bioavailability, hinder their effective medical applications. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical properties. Incorporation of fluorine atom(s) at appropriate positions often improves the metabolic stability of the parent compound, increasing its bioavailability, and enhances its binding affinity to therapeutic targets, making fluorine a highly valuable element in modern drug development. Furthermore, amino functional groups may improve the water solubility and bioavailability of the compounds. Building on these principles, our strategy focused on introducing groups containing mono-, di-, and trifluoroethylamine or fluorinated aniline moieties into cannabinoids to improve their pharmacokinetic and pharmacological profiles.

Methods: Mannich-type reaction was applied, using commercially available 2-fluoroethylamine, 2,2-difluoroethylamine, 2,2,2-trifluoroethylamine, 3-fluoroaniline and 4-fluoroaniline as reagents. One or two oxazine rings with fluorine-containing side chains were condensed to the aromatic core of the cannabinoids, and the formation of mono- or disubstituted derivatives was controlled by the appropriate choice of reaction conditions. The biological activity of the derivatives was investigated in various relevant fields.

Results and conclusion: Our findings indicate that aliphatic modifications positively influence pharmacokinetic parameters, including absorption, in contrast to aromatic groups, which increase lipophilicity and lead to decreased bioavailability. Among the modifications, the monosubstituted derivatives containing a single oxazine ring with an aliphatic fluorine-containing side chain, especially the mono- and trifluoroethyl moieties, proved to be the most promising. These modifications appeared particularly advantageous in the CBG series compared to the properties of the CBG parent compound. This may suggest that the presence of a phenolic OH group is beneficial for biological activity. Some of the derivatives showed anticancer potential against various tumor cell lines, while others modulated sebaceous lipogenesis, and certain compounds exhibited a notable antimalarial effect.

Background: Many people who engage in heavy cannabis use do not seek treatment, and those who do are often met with long treatment wait times or high cost of services. Online treatment programs reduce barriers to accessing treatment in a timely manner. Online cannabis use treatment programs are effective, showing moderate effect sizes, particularly with text-based therapist support. Literature suggests brief therapist-guided introductions (i.e., self-completed interventions offered with the support of a therapist) informed by Motivational Enhancement Therapy (MET) may help to bolster and maintain program gains. The current evaluation of MET-informed therapist-guided introduction was conducted with a sample of Canadians who report heavy cannabis use, using a new Canadian version of CANreduce, an online treatment program for heavy cannabis use.

Method: The intervention was pre-registered on clinicaltrials.gov for traceability (ID: NCT04965012). Participants (N = 152) were randomized into one of three conditions: MET-therapist guided introduction plus 6-week, online, self-guided treatment program; non-MET research assistant introduction plus 6-week, online, self-guided treatment program; or a psychoeducational control condition. Module content to reduce cannabis use was informed by cognitive behavioural therapy and motivational interviewing approaches. Participants completed assessments at baseline, end of treatment (i.e., 6 weeks), and at follow up (i.e., 10 weeks). Data were analyzed using Generalized Estimating Equations.

Results: All participants reduced their cannabis consumption frequency (use days in the past week), as well as cannabis-related problems, at end of treatment and follow up. Participants in the MET-therapist condition showed significantly greater reductions in quantity of cannabis used over time compared to the waitlist control. Participants in the non-MET research assistant condition showed significantly greater reductions in cannabis problems compared to waitlist control. There were no significant differences between MET-therapist guided conditions and non-MET research assistant conditions. There was no significant effect of condition on cannabis consumption days in the past week, anxiety, depression or quality of life.

Conclusion: The present study provides preliminary support for the CANreduce program in addition to the MET-therapist guided introduction.