Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Public Attitudes Toward the Drug Enforcement Administration’s Proposal to Reschedule Marijuana: A Cross-Sectional Mixed-Methods Analysis

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“Introduction: On May 21, 2024, the Drug Enforcement Administration (DEA) published a proposed rule to reschedule marijuana from schedule I to III under the Controlled Substance Act (CSA), followed by a 60-day open comment period. The purpose of this study was to analyze the public attitudes regarding the proposed rule and identify trends based on time of comment submission and recurring arguments throughout the comments.

Methods: This was an observational, cross-sectional, mixed-methods study. Comments from the proposal were stratified according to the submission date as early (May 21 to June 11), mid- (June 12 to July 2), and late (July 3-22) respondents. Investigators were assigned an equal number of comments to code as in favor of, against, or no clear position on rescheduling. Comments were further coded based on type of comment (form letters, personal anecdotes), rationale for comment (racism, decriminalization, safety, and economic factors), and whether descheduling was favored. Chi-square tests were used to analyze categorical data. A random sample of comments was selected to assure a 5% margin of error.

Results: More than 42,000 comments were submitted. Of these, 380 comments were selected and coded, with 42% (n = 158) in support of rescheduling, 55% (n = 211) against rescheduling, and 2.9% (n = 11) with no clear position. Of all comments coded, 71% wanted to go further and were in support of descheduling. The early responses consisted of a majority in favor of rescheduling, while the mid- and late responses consisted of more comments against rescheduling (X 2 [2, N = 369] = 35.8, p < 0.00001). Of the comments against rescheduling, a large majority supported descheduling (X 2 [2, N = 265] = 32.0, p < 0.0001). As for comment structure, 69% (n = 263) of all comments coded were form letters, while 8.4% (n = 32) were personal anecdotes.

Conclusion: The number of comments in support of rescheduling decreased with time, only dominating the early respondent wave. Despite a larger number of negative attitudes toward the DEA’s proposed rule of rescheduling marijuana from schedule I to III, a majority of comments supported taking a step further to deschedule marijuana all together.”

https://pubmed.ncbi.nlm.nih.gov/40655530/

“The study’s findings suggest that future cannabis policy discussions may need to address not just rescheduling, but potentially more far-reaching reforms to align with evolving public sentiment. As the conversation around marijuana regulation continues, policymakers will need to carefully balance public health and safety concerns with growing calls for increased access and reduced criminalization.”

https://karger.com/mca/article/8/1/117/928534/Public-Attitudes-Toward-the-Drug-Enforcement

Exploring the Potential of Phytocannabinoids Against Multidrug-Resistant Bacteria

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“The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a critical threat to global health, creating an urgent need for novel antimicrobial agents.

In this study, we evaluated a small library of natural and semisynthetic phytocannabinoids against a broad panel of MDR Gram-positive bacterial strains, evidencing very good activity in the low µM range.

We provide evidence of the antibacterial activity of the two separated enantiomers of cannabidiol, offering novel insights into the stereochemical aspects of their bioactivity.

To investigate the possible molecular targets and clarify the mechanism of action, we employed Inverse Virtual Screening (IVS), a computational approach optimized for predicting potential protein-ligand interactions, on three selected MDR bacterial species. Interestingly, key targets belonging to important bacterial metabolic pathways and defense mechanisms were retrieved, and the results were used to rationalize the observed biological activities.

To the best of our knowledge, this study marks the first application of IVS to microorganisms, offering a novel strategy for identifying bacterial protein targets. The results pave the way for future experimental validation, structure-based drug design, and the development of novel antibacterial agents.”

https://pubmed.ncbi.nlm.nih.gov/40647911/

“These findings suggest that these phytocannabinoids likely exert their antibacterial effects via multi-target inhibition, interfering with multiple essential bacterial pathways.”

https://www.mdpi.com/2223-7747/14/13/1901

Medicinal cannabis for tics in adolescents with Tourette syndrome

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“Medicinal cannabis has been trialled for Tourette syndrome in adults, but it has not been studied in adolescents. This open-label, single-arm trial study evaluated the feasibility, acceptability and signal of efficacy of medicinal cannabis in adolescents (12-18 years), using a Δ9-tetrahydrocannabinol:cannabidiol ratio of 10:15, with dose varying from 5 to 20 mg/day based on body weight and response.

The study demonstrated feasibility of recruitment, acceptability of study procedures, potential benefits and a favourable safety profile, with no serious adverse events. Commonly reported adverse events were tiredness and drowsiness, followed by dry mouth.

Statistically significant improvement was observed in parent and clinician reports on tics (paired t-test P = 0.003), and behavioural and emotional issues (paired t-test P = 0.048) and quality of life as reported by the parent and young person (paired t-test P = 0.027 and 0.032, respectively). A larger-scale, randomised controlled trial is needed to validate these findings.”

https://pubmed.ncbi.nlm.nih.gov/40636988/

https://www.cambridge.org/core/journals/bjpsych-open/article/medicinal-cannabis-for-tics-in-adolescents-with-tourette-syndrome/1A788DF6DE778600989CD90AF7A604D0

Acute Effects of Oral Cannabinoids on Sleep and High-Density EEG in Insomnia: A Pilot Randomised Controlled Trial

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“Cannabinoids, particularly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have gained popularity as alternative sleep aids; however, their effects on sleep architecture and next-day function remain poorly understood.

Here, in a pilot trial, we examined the effects of a single oral dose containing 10 mg THC and 200 mg CBD (THC/CBD) on objective sleep outcomes and next-day alertness using 256-channel high-density EEG in 20 patients with DSM-5 diagnosed insomnia disorder (16 female; mean (SD) age, 46.1 (8.6) years).

We showed that THC/CBD decreased total sleep time (-24.5 min, p = 0.05, d = -0.5) with no change in wake after sleep onset (+10.7 min, p > 0.05) compared to placebo. THC/CBD also significantly decreased time spent in REM sleep (-33.9 min, p < 0.001, d = -1.5) and increased latency to REM sleep (+65.6 min, p = 0.008, d = 0.7). High-density EEG analysis revealed regional decreases in gamma activity during N2 sleep, and in delta activity during N3 sleep, and a regional increase in beta and alpha activity during REM sleep. While there was no observed change in next-day objective alertness, a small but significant increase in self-reported sleepiness was noted with THC/CBD (+0.42 points, p = 0.02, d = 0.22). No changes in subjective sleep quality, cognitive performance, or simulated driving performance were observed.

These findings suggest that a single dose of cannabinoids, particularly THC, may acutely influence sleep, primarily by suppressing REM sleep, without noticeable next-day impairment (≥ 9 h post-treatment).”

https://pubmed.ncbi.nlm.nih.gov/40631525/

“This study is the first to use high-density EEG to explore the acute effects of oral THC/CBD on objective sleep outcomes in individuals with insomnia. A single oral dose significantly reduced total sleep time and REM sleep, without impairing next-day alertness.”

https://onlinelibrary.wiley.com/doi/10.1111/jsr.70124

Long-term cannabinoid therapy can ameliorate chronic sleep deprivation-induced behavioral and neuroinflammatory changes in mice

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“Endocannabinoid system is an important contributor to body’s immune responses which are significantly impaired by chronic sleep deprivation (cSD). Although cannabinoids can modulate the endocannabinoid system, most are understudied, especially regarding cSD.

To investigate the therapeutic potential of CBD, CBG, CBC and their combinations, current study analyzed cSD-induced memory impairment, depression, microglial responses, cytokine profile and therapeutic effects of cannabinoid treatments using behavioral test and ELISA. Furthermore, molecular docking of these cannabinoids was performed to deduce the binding affinity with cannabinoid receptors and possible entrouge effects.

The results showed that memory impairment and depression were more evident in cSD groups. Moreover, microglial activation and pro-inflammatory polarization was also more evident and was supported by increased pro-inflammatory cytokine concentrations in cSD groups.

These changes were significantly reversed the cannabinoid groups but the combination of CBD + CBC was more effective than other treatments in reversing these cSD-induced behavioral and neuroinflammatory changes. Whereas, the molecular docking results also corroborated with the neuroimmunological changes observed in the current study, pointing towards the possible therapeutic role.

SIGNIFICANCE STATEMENT: Chronic SD employs microglial activation/polarization, to exert behavioral impairments and neuroinflammation.

This study signifies the therapeutic potential of proper sleep and cannabinoid intake.”

https://pubmed.ncbi.nlm.nih.gov/40628367/

“This study demonstrates the therapeutic efficacy of cannabinoid treatments in ameliorating cSD-induced behavioral and neuroinflammatory alterations. Notably, a multiple-compound treatment of CBD and CBC exhibited superior effectiveness compared to single-compound treatments. These findings suggest potential avenues for developing effective interventions against cSD-induced detrimental changes.”

https://www.sciencedirect.com/science/article/abs/pii/S0304394025002022?via%3Dihub

Treatment of Migraine With Phytocannabinoids, the Involvement of Endocannabinoids in Migraine, and Potential Mechanisms of Action

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“The American Migraine Foundation estimates that over 39 million Americans and over 1 billion people worldwide suffer from some form of migraine. Treatment of migraine generally falls into two categories: treatment of attacks once they have begun, and prophylactic prevention, including lifestyle changes. The use of phytocannabinoids to reduce both the frequency and severity of migraine is widely documented in scientific, grey, and popular literature. This review provides descriptions of both preclinical and clinical studies involving the treatment of migraines with phytocannabinoids as well as the involvement of endocannabinoids and endocannabinoid-like compounds in migraine pathology, including the receptors and associated mechanisms. Currently unanswered questions and areas for further exploration are discussed.”

https://pubmed.ncbi.nlm.nih.gov/40630421/

“The clinical studies published to date strongly suggest that phytocannabinoids are useful for mitigating migraine pain and for migraine prophylaxis. Further, studies show the potential for endocannabinoid and endocannabinoid-like compounds in migraine treatment.”

https://onlinelibrary.wiley.com/doi/10.1155/prm/7181066

“Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”

https://pubmed.ncbi.nlm.nih.gov/15159679/

Acute and chronic effects of medicinal cannabis use on anxiety and depression in a prospective cohort of patients new to cannabis

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“Introduction: Medicinal cannabis has mixed evidence for treating anxiety and depression, yet patients frequently use it as a treatment. This observational study evaluated the effects of medicinal cannabis initiation in adults with clinically significant anxiety and/or depression over a 6-month period.

Methods: Adults with clinically significant anxiety and/or depression initiating medicinal cannabis use in Maryland, USA completed ecological momentary assessment (EMA) and longitudinal follow-up evaluations. Hospital Anxiety and Depression Scale (HADS) assessments were completed at baseline and 1, 3, and 6 months after medicinal cannabis initiation. EMA measures were completed at baseline and daily for 8 weeks after cannabis initiation with measures collected before each cannabis use and at time of expected peak effect. Changes in anxiety and depression were evaluated using linear mixed effect models.

Results: Significant decreases from baseline in anxiety and depression were observed, with mean scores dropping below clinically significant levels within three months of initiation. EMA data indicated that most participants selected THC-dominant cannabis and acute reductions in anxiety, depression, and perceived driving ability along with increased ratings of feeling “high”. Acute effects were dose-dependent: 10-15 mg of oral THC and at least 3 puffs of vaporized cannabis yielded the most robust reductions in anxiety and depression.

Conclusions: Initiation of THC-dominant medicinal cannabis was associated with acute reductions in anxiety and depression, and sustained reductions in overall symptom severity over a 6-month period. Controlled clinical trials are needed to further investigate the efficacy and safety of medicinal cannabis for acute anxiety and depression symptom management.”

https://pubmed.ncbi.nlm.nih.gov/40623642/

“In this prospective, observational study, medicinal cannabis use was associated with significant decreases in self-reported anxiety and depression compared with pre-cannabis use initiation baseline assessments among individuals with clinically significant anxiety and/or depression. Reductions in anxiety and depression were observed acutely following individual episodes of cannabis use and overall symptom reductions were sustained over the six-month period of observation.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032725012716?via%3Dihub

Evaluating the impact of cannabis oil for autistic children with and without concomitant medications: Insights from an open-label study

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“Background: Although only two drugs are FDA approved for autism spectrum disorder (ASD), clinical practice treatment includes off-label use of medications to address the troubling symptoms of ASD. Several trials showed the beneficial effects of medical cannabis for alleviating symptoms of ASD. However, data are lacking regarding its safety and effectiveness as a single agent compared to add-on therapy.

Aims: To compare the safety and effectiveness of medical cannabis as a monotherapy and add-on therapy in autistic children.

Methods: An open-label trial recruiting autistic children was performed and treated with medical cannabis oil with a THC:CBD ratio of 1:20, respectively. Tests were conducted at baseline and after 6 months of therapy. A secondary analysis was done to compare physical and behavior parameters, using tests such as Autism Diagnostic Observation Schedule and Wechsler tests in the two groups.

Results: Out of 109 participants, 81 completed the treatment. Thirty received cannabis as add-on therapy to a pre-existing treatment, whereas 51 received cannabis as monotherapy, with no observed differences in baseline characteristics between the groups. The mean maximal CBD dose was 3.1 mg/kg/day in the monotherapy group, compared to 2.8 mg/kg/day in the add-on group (p = 0.40). In patients treated with drugs for psychosis, the mean maximal dose was 2.48 mg/kg/day (p = 0.12). No differences were observed in most physical and behavioral parameters. In addition, no differences in CBD blood levels were observed.

Conclusions: Add-on cannabis therapy is as safe as monotherapy treatment, without significant differences in efficacy.”

https://pubmed.ncbi.nlm.nih.gov/40613426/

https://journals.sagepub.com/doi/10.1177/02698811251332841

Oral Cannabis for Taxane-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Study

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“Introduction: Taxane-induced peripheral neuropathy (TIPN) is experienced by most patients with breast cancer, and there is no efficacious treatment. In pre-clinical studies, co-administration of two constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduces TIPN. 

Materials and Methods: The goal of this 8-week, double-blind, randomized pilot study, conducted from 2019 to 2021, was to test the feasibility and tolerability of oral cannabis (100 mg CBD: 5 mg THC, TID) relative to placebo on pain resulting from TIPN. Participants with painful TIPN completed daily questionnaires online about their pain, sleep, and medication use, and weekly questionnaires on neuropathy. 

Results: All participants (12 women; 51 ± 6 years) randomized to placebo (n = 6) or active (n = 6) cannabis capsules completed the trial. Participants in both medication groups requested dose reductions (mean ± SEM capsules/day: placebo: 2.4 ± 0.4; active: 2.0 ± 0.4). In a preliminary evaluation of efficacy, measures of pain, pain interference, sleep, and functional well-being significantly improved over time (p < 0.03), but participants receiving cannabis had significantly higher ratings of neuropathy at each week (p < 0.035) and lower ratings of functional well-being in the last 3 weeks of treatment compared with participants receiving placebo (p < 0.02). Similarly, cannabis significantly worsened ratings of sleep and pain interference relative to placebo (p < 0.05). 

Discussion: This study demonstrates that: (1) double-blind, placebo-controlled testing of cannabis capsules in this dose range is feasible and well tolerated in women with TIPN and (2) ratings of pain, neuropathy, and well-being significantly improved over 8 weeks, but cannabis significantly worsened several endpoints relative to placebo. These findings highlight the necessity of placebo control when assessing the therapeutic utility of cannabis. Although there was no signal of efficacy herein, a fully powered study testing a range of cannabis doses for TIPN is warranted, given its impact on most patients with breast cancer, promising pre-clinical data, and the widespread use of cannabis among patients with cancer.”

https://pubmed.ncbi.nlm.nih.gov/40611810/

https://www.liebertpub.com/doi/10.1089/can.2025.0028

Cannabidiol interactions with Δ-9-tetrahydrocannabinol on antinociception after carrageenan-induced inflammatory pain in male and female rats

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“Cannabis products used for pain typically contain Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) in varied amounts, but data on the effects of specific cannabinoid formulations on different pain types are lacking.

This study used the carrageenan-induced inflammatory pain model to test oral Δ9-THC, CBD, or their combination on acute edema and pain hypersensitivity.

Male and female Sprague-Dawley rats (n = 10-14 per sex/group) were pretreated (1 hour) with vehicle (sesame oil), Δ9-THC (1, 3, and 10 mg/kg, p.o.), CBD (10, 30, 100 mg/kg, p.o.), or select doses of Δ9-THC + CBD combinations prior to an intraplantar λ-carrageenan injection into the hind paw.

The nonsteroidal anti-inflammatory drug ketoprofen (10 and 20 mg/kg i.p.) or its vehicle (1:1:18 ethanol:Cremophor EL:saline [Millipor Sigma]) was administered to a separate group as a positive control. Measurements were conducted at baseline and 1, 3, and 5 hours after carrageenan injection. Carrageenan produced edema and hypersensitivity to radiant heat (hyperalgesia) and mechanical pressure (allodynia).

Δ9-THC alone sex- and dose-dependently decreased hyperalgesia and allodynia but not inflammation, with effects of Δ9-THC being greater in females than males, and the lowest Δ9-THC dose was proinflammatory in males. CBD alone did not affect pain sensitivity but had modest anti-inflammatory effects in males. Isobolographic and dose addition analyses indicated Δ9-THC + CBD was subadditive relative to Δ9-THC alone.

These data demonstrate that prophylactic oral Δ9-THC alleviates acute inflammatory pain with sex-dependent effects, and CBD diminishes Δ9-THC antinociception when combined.

The findings suggest oral Δ9-THC is superior to CBD or combined Δ9-THC + CBD for acute inflammatory pain.

SIGNIFICANCE STATEMENT: Despite the popularity of cannabis for pain management, empirical data on how specific cannabinoid formulations affect acute inflammatory pain are limited. This study in rats found that pure Δ-9-tetrahydrocannabinol (Δ9-THC) formulations were most effective at improving inflammatory pain compared to pure cannabidiol or Δ9-THC + cannabidiol combinations, and females were more sensitive than males to the antinociceptive effects of Δ9-THC.”

https://pubmed.ncbi.nlm.nih.gov/40609153/

https://jpet.aspetjournals.org/retrieve/pii/S0022356525398381