Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Treatment with a botanical mixture of cannabidiol:Δ9-tetrahydrocannabinol enhances microglial phagocytosis and shapes amyloid plaques in a mouse model of Alzheimer’s disease

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“The potential use of phytocannabinoids in neurodegenerative disorders is currently under intense investigation based on their potential anti-inflammatory, antioxidant, and neuroprotective effects.

Here, we tested the effects of chronic (28 days) treatment with a complex botanical mixture of purified cannabidiol:Δ9-tetrahydrocannabinol (CBD:THC, 99:1) in male 5xFAD mice, a murine model of Alzheimer’s disease that recapitulates amyloid pathology. Effects of exposure to this cannabinoid mixture were evaluated using behavioral tests (elevated plus maze for anxiety, tail suspension for depression-like behavior, rotarod for motor coordination, open field for locomotor activity, and novel object recognition for memory), quantification of protein expression (IL-1β, CD40, TREM2, COX2), assessment of functional parameters (microglial phagocytic activity by flow cytometry), and in vivo multiphoton microscopy (time-course of changes of neuritic plaque structural features). Twice daily dosing with 50 mg/kg subcutaneously (s.c.) significantly reduced locomotion, increased anxiety- and depression-like behaviors and had no effect on memory and motor coordination.

In vivo imaging experiments suggest that the CBD:THC treatment enhanced microglial phagocytic activity on amyloid plaques; this effect was observed both in plaque features (multiphoton microscopy measurements) as well as in microglia (flow cytometry data). Exposure to CBD:THC induced significant changes in in vivo microglia-amyloid interactions, increasing phagocytic activity and reducing the amyloid peptide accumulation in the neuritic plaques.

Thus, CBD:THC (99:1) may be a promising treatment to reduce amyloid pathology, though caution should be noted due to the behavioral alterations observed, i.e., increased anxiety- and depression-like behaviors as well as decreased locomotion.”

https://pubmed.ncbi.nlm.nih.gov/41389629

https://www.sciencedirect.com/science/article/pii/S0753332225010960?via%3Dihub


Investigating the effectiveness and adverse events of medicinal cannabis for patients with muscle spasticity or spasms

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“Appropriate treatment of muscle spasticity and spasms is important as these conditions may significantly impair patients’ quality of life. Conventional pharmacological treatments for these conditions have poor effectiveness and/or tolerability.

Cannabis is being explored as a treatment.

This was a longitudinal study of patient use of different cannabis products. Data was collected from patient surveys, clinic records, and changes in Patient Reported Outcome Measures Information System 29-Item scores over time. Patient-reported responses on health-related quality of life adverse events (n = 150) and outcomes (n = 78) from treatment for spasticity or spasms were analyzed. No improvements in physical functioning were observed for either group of patients across all product types. However, patients with spasticity who were using cannabidiol-only products experienced an improvement in sleep disturbance, fatigue, pain interference, and pain intensity.

Patients with spasms who were using balanced, cannabidiol-dominant, or tetrahydrocannabinol-dominant products also experienced improvements in these 4 outcomes. Commonly reported adverse events were dry mouth, drowsiness, fatigue, dizziness, and nausea. Despite no observation of improvement in physical functioning, the results suggest that cannabis may help relieve some of the secondary complications associated with these conditions, such as poor sleep and pain.

SIGNIFICANCE STATEMENT: This longitudinal study highlights differential benefits across cannabis product types, with cannabidiol-only formulations aiding spasticity-related symptoms and tetrahydrocannabinol- or cannabidiol-dominant products benefiting those with spasms.

These findings support the potential of cannabis as a potential therapy to improve health-related quality of life in patients with limited options from conventional pharmacological treatments.”

https://pubmed.ncbi.nlm.nih.gov/41386046

https://jpet.aspetjournals.org/article/S0022-3565(25)40293-6/abstract


Cannabis Use and Nicotine Vaping Cessation Outcomes: A Secondary Analysis of a Randomized Clinical Trial

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“Importance: Cannabis use is prevalent among adolescents and young adults who vape nicotine. It is not known if cannabis use affects nicotine vaping cessation success.

Objective: To assess whether baseline frequency of cannabis use or cannabis use disorder (CUD) symptom severity was associated with nicotine vaping cessation in a randomized clinical trial.

Design, setting, and participants: This secondary analysis of a randomized clinical trial with youth who vaped nicotine recruited at a single site in Massachusetts from June 2022 to May 2024. The trial included 3 groups receiving 12 weeks of varenicline treatment and placebo (both double-masked, paired with counseling), as well as single-masked referral to texting-app-based nicotine vaping cessation support (enhanced usual care [EUC]). Eligible participants were aged 16 to 25 years who reported vaping nicotine regularly and did not smoke tobacco.

Exposure: Baseline cannabis use was assessed via self-reported number of days of cannabis use per week and with Cannabis Use Disorder Identification Test (CUDIT) scores.

Main outcomes and measures: Biochemically verified 7-day point prevalence nicotine vaping abstinence at week 12. Logistic regression models estimated associations between baseline cannabis use and vaping abstinence. Interaction terms were evaluated to examine whether cannabis use moderated the effect of varenicline on nicotine abstinence.

Results: Among the 261 participants randomized to nicotine vaping cessation treatment (mean [SD] age, 21.5 [2.0] years; 139 female [53%]), 28% (73 participants) reported no past-month cannabis use, 38% (100 participants) reported using cannabis more than 0 and less than 4 d/wk, and 30% (78 participants) reported using cannabis 4 to 7 d/wk. Cannabis use frequency was not significantly associated with nicotine vaping cessation (eg, 4 to 7 d/wk use vs no use: adjusted odds ratio [aOR], 1.14; 95% CI, 0.51-2.57; overall P = .20). Nor did cannabis frequency modify the effect of varenicline (eg, abstinence varenicline vs placebo or EUC among those with 4 to 7 d/wk use: aOR, 8.47; 95% CI, 2.78-28.25; vs among those with no use: aOR, 5.60; 95% CI, 1.97-17.06; overall interaction P = .32). Findings were similar for CUD symptom severity.

Conclusions and relevance: Among adolescents and young adults attempting to reduce or stop nicotine vaping, baseline cannabis use was not associated with nicotine vaping abstinence. Varenicline proved helpful for nicotine vaping cessation regardless of cannabis use, indicating that co-use of cannabis may not represent a barrier to successful nicotine vaping cessation treatment.”

https://pubmed.ncbi.nlm.nih.gov/41385228

“Findings indicate that regular cannabis or alcohol use is not expected to diminish the effectiveness of offering varenicline for nicotine vaping cessation in youth.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2842688

Cannabis use and cardiometabolic risk in schizophrenia

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“Purpose: Metabolic syndrome (MetS) is common in schizophrenia and drives cardiovascular risk. While cannabis use and potency are increasing, the impact of cannabis on cardiometabolic health in schizophrenia remains unclear. This study assessed the association between objectively measured cannabis use and MetS prevalence in a large schizophrenia cohort.

Methods: We conducted a cross-sectional analysis of 988 participants with DSM-IV schizophrenia from the CATIE study. Cannabis use was measured via hair testing for tetrahydrocannabinol (THC), the gold standard for long-term use detection. MetS was defined per International Diabetes Federation criteria using physical and biochemical data. Multivariable logistic regression, adjusting for demographic, clinical, and lifestyle confounders, assessed the association between THC use and MetS.

Results: THC-positive participants (14.8 %) exhibited a significantly lower prevalence of MetS compared to non-users (42.5 % vs. 60.5 %, p < 0.001). After adjusting for confounders including age, sex, ethnicity, smoking, and other substance use, cannabis use remained independently associated with reduced odds of MetS (adjusted OR 0.64, 95 %CI 0.44-0.93, p = 0.02). Among MetS components, cannabis users had significantly lower odds of elevated waist circumference after adjustment (adjusted OR 0.61, 95 %CI 0.41-0.91, p = 0.02). Cannabis use was also associated with lower weight, BMI and triglycerides and higher HDL in unadjusted analyses. No significant differences were found in blood pressure or fasting glucose.

Conclusions: In schizophrenia, cannabis use was associated with lower rates of both metabolic syndrome and central obesity. While these findings support emerging evidence of metabolic differences in cannabis users, the cross-sectional design precludes conclusions regarding causality. Longitudinal studies are needed to clarify long-term metabolic effects and guide targeted interventions.”

https://pubmed.ncbi.nlm.nih.gov/41265115

“Cannabis use is associated with better cardiometabolic health in the general population, with users showing lower fasting insulin and glucose levels, reduced waist circumference, lower BMI, reduced systolic blood pressure (SBP) and higher high-density lipoprotein (HDL) cholesterol compared to non-users.”

“Growing evidence suggests cannabis users with psychotic disorders may have better metabolic health compared to non-users.”

“In summary, our findings demonstrate a significant association between cannabis use and a lower prevalence of metabolic syndrome in individuals with schizophrenia.”

https://linkinghub.elsevier.com/retrieve/pii/S0920996425004037

Bioreactor-Based Suspension Cultures of Cannabis sativa for Enhanced Production of Anti-Inflammatory Cannabinoid Derivatives

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“Cannabis sativa synthesizes diverse cannabinoids with significant pharmacological value, but existing suspension cultures show low metabolite yields and limited scalability.

This study establishes bioreactor-based cell suspension system to enhance cannabinoid biosynthesis in C. sativa. Petiole explants cultured on MS medium with 4 mg/L BAP and 0.01 mg/L NAA produced 95.83 ± 0.74% friable callus. Suspension cultures accumulated 352.29 ± 3.90 g/L fresh biomass in 28 days, showing 22.4-fold increase upon scale-up in stirred-tank bioreactor.

Methanolic extracts (60 °C) showed strong anti-inflammatory activity, reducing TNF-α and IL-6 by 88.40 ± 0.87 and 92.03 ± 1.55% at 30 μg mL-1 without cytotoxicity. Metabolomic profiling identified putative cannabinoid derivatives, with THCA-C1 (0.05%) exhibiting highest binding affinity (-8.4 kcal/mol) to inflammatory targets based on docking and dynamics analyses.

Overall, these results provide the first evidence for scalable cannabinoid biosynthesis in bioreactor-grown C. sativa cell suspensions, underscoring their potential for sustainable production of anti-inflammatory therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/41359809

https://pubs.acs.org/doi/10.1021/acs.jafc.5c10683


Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Importance: Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective: To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, setting, and participants: This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure: Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main outcomes and measures: Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results: Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = -3.53; 95% CI, -6.68 to -0.04; P = .03).

Conclusions and relevance: In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/41359313

“These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414

Multifaced roles of cannabinoid therapy in cancer: balancing analgesia, antitumor potential, and systemic toxicity

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“Introduction: Cannabinoids hold promise in oncology for symptom relief and antitumor effects, though concerns about safety and efficacy persist. This study assessed the impact of JWH-182 and phytocannabinoids NC1 – Cannabixir® Medium dried flowers and NC2 – Cannabixir® THC full extract, in a murine breast cancer model with paclitaxel-induced peripheral neuropathy (CIPN).

Methods: Female BALB/c mice with breast tumors received paclitaxel alone or combined with cannabinoids, and outcomes included pain sensitivity, tumor progression (imaging and histopathology), cachexia (body weight, food intake, imaging), as well as hematological and organ toxicity profiles.

Results: All cannabinoids alleviated neuropathic pain, with NC1 most effective for central and thermal protection (72% and 100%, p < 0.0001), NC2 showing strong central and mechanical benefit (>60% and >33%), and JWH-182 intermediate (∼50%). Tumor growth was not significantly altered, but metastasis incidence was 41.7% for NC1, 58.3% for NC2, compared with 70% for PTX, suggesting antitumoral activity. Effects on cachexia were modest, JWH-182 tended to improve food intake, whereas NC1 and NC2 reduced it, yet body weight remained stable and significant muscle loss was observed only with NC2 (p < 0.05). Hematology showed immunomodulatory effects, with cannabinoids reversing lymphopenia (p = 0.0005), raising monocytes and neutrophils, and partly restoring platelets. Toxicity was highest with NC2 (renal and hepatic injury), moderate with NC1, and lowest for kidney with JWH-182 but with greater hepatic inflammation.

Conclusion: Cannabinoids show potential in oncology by relieving CIPN and influencing tumor dynamics, with mostly neutral effects on cachexia. GMP-certified formulations enhance translational value, though safety concerns warrant further study.”

https://pubmed.ncbi.nlm.nih.gov/41357884

“Cannabinoids have emerged as promising agents in oncology for both symptom relief and potential antitumor effects. By acting on cannabinoid receptors 1 and 2 (CB1R, CB2R), Tetrahydrocannabinol (THC) and Cannabidiol (CBD) help regulate pain, appetite, and inflammation, making them effective in managing CIPN, cancer pain, and cachexia.

Preclinical studies also suggest that cannabinoids can inhibit tumor growth, metastasis, angiogenesis, and reverse chemoresistance, with potential to enhance chemotherapy efficacy and reduce its toxicity.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1691893/full

UK Medical Cannabis Registry: An Updated Analysis of Cannabis-Based Medicinal Products for Multiple Sclerosis

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“Introduction: Multiple sclerosis (MS) is a neurodegenerative disease presenting with a wide range of motor, sensory, and psychiatric symptoms. Although nabiximols is licensed for MS-induced spasticity, cannabis-based medicinal products (CBMPs) have also displayed promising therapeutic potential for managing pain, sleep, and anxiety. Therefore, further evaluation of CBMP treatment for MS is warranted. This study aimed to assess the efficacy and tolerability of CBMP treatment in patients with MS by investigating changes in MS-specific and general health-related patient-reported outcome measures and adverse events.

Methods: This was a prospective case series including patients with MS enrolled on the UK Medical Cannabis Registry. Changes in MS Quality of Life-54 (MSQOL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scores were assessed from baseline up to 24 months. The prevalence and severity of all adverse events were also assessed.

Results: This study included 203 patients, of whom 47.29% (n = 96) were female and 80.79% (n = 164) had prior cannabis exposure. Improvements in the MSQOL-54 subscales: change in health, energy, health distress, pain, physical function, and physical role limitations, along with improvements in SQS and EQ-5D-5L scores, were seen at all follow-up times compared to baseline (p < 0.050). A total of 278 adverse events were reported by 26 patients (12.81%). Most adverse events were mild (n = 91, 32.73%) or moderate (n = 138, 49.64%) in severity, with fatigue (n = 27, 13.30%) and spasticity (n = 17, 8.37%) being the most common.

Conclusion: CBMP treatment over 24 months was associated with improvements in health-related quality of life and was well tolerated in patients with MS. Future randomised controlled trials with more representative study populations are needed to establish causal relationships.”

https://pubmed.ncbi.nlm.nih.gov/41357430

“There is increasing evidence for the involvement of the endocannabinoid system (ECS) in modulating inflammatory and neurodegenerative processes.”

“Through interactions with the ECS, THC and CBD have displayed analgesic, muscle relaxant, neuroprotective, and anti-inflammatory properties in preclinical and clinical studies.”

“Therefore, cannabis-based medicinal products (CBMPs) containing these phytocannabinoids show promise for managing MS symptoms.”

“In conclusion, this observational study found CBMP treatment was associated with improvements in many HRQoL measures, including pain and sleep in patients with MS. Also, CBMP use over 2 years was generally well tolerated.”

https://karger.com/mca/article/8/1/201/938322/UK-Medical-Cannabis-Registry-An-Updated-Analysis

Aromatisation-based extract engineering of Cannabis sativa L. Unveils rare cannabinoids with anticancer potential

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“Cancer remains a major global health challenge, necessitating new, effective therapies. Phytocannabinoids from Cannabis sativa L. show significant anticancer potential, yet their natural scarcity limits research and development.

This study presents an innovative extract engineering approach to generate rare varin-type cannabinoids from abundant precursors. Through this strategy, nine cannabinoid analogues were synthesised, including four rare varin-type compounds, and screened against five human cancer cell lines.

Among them, cannabinovarin (CBNV) and Δ6a,10a-THCV exhibited potent cytotoxicity against breast (MCF-7) and colon (HCT-116) cancer cells, with IC50 values of 15-30 µM. Mechanistic investigations revealed apoptosis induction via mitochondrial membrane disruption and reactive oxygen species generation.

These findings establish extract engineering as a rapid and efficient route to access rare cannabinoids, highlighting CBNV and Δ6a,10a-THCV as promising anticancer leads for further mechanistic and in vivo evaluation.”

https://pubmed.ncbi.nlm.nih.gov/41355760

https://www.tandfonline.com/doi/full/10.1080/14786419.2025.2595528

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

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“In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings.

Cannabinoids have been suggested and shown to be effective in the treatment of various conditions.

In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis.

Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions.”

https://pubmed.ncbi.nlm.nih.gov/32708138

“Dysregulation of the endocannabinoid system has been implicated in several diseases, including cancer.”

“Based on the preliminary evidence in various models, it appears that cannabinoids target key signaling pathways involved in all the hallmarks of cancer. Additionally to the cannabinoids, a large number of terpenes and flavonoids, some of them also present in cannabis, exhibit cytotoxicity against a variety of cancers.”

“Considering all the available literature at this time, much stronger experimental evidence (obtained in vitro, in vivo and even in a few clinical trials) support that THC and cannabidiol (CBD) have better anticancer activity than for the other cannabinoids.”

https://www.mdpi.com/2072-6694/12/7/1985