Category Archives: THC (Delta-9-Tetrahydrocannabinol)

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

A Randomized Controlled Trial of the Safety and Efficacy of Dronabinol for Agitation in Alzheimer’s Disease

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“Importance: Agitation in Alzheimer’s disease (AD) is a great source of distress for patients and caregivers and a major public health burden. Current treatments are only modestly effective and many have safety issues including mortality risk. Novel therapeutic options are needed.

There is preliminary evidence for the safety and efficacy of dronabinol (tetrahydrocannabinol, THC) for agitation in AD.

Objective: Assess the safety and efficacy of dronabinol (THC) to decrease agitation in AD.

Design: THC-AD was a 3-week randomized parallel double-blind placebo-controlled clinical trial, conducted between 2017 and 2024.

Setting: 5 inpatient and outpatient academic clinical research centers in the Eastern U.S.

Participants: Volunteer sample of 75 participants meeting inclusion criteria for agitation of AD (International Psychogeriatric Association Provision Criteria) with Neuropsychiatric Inventory Clinician Version Agitation or Aggression (NPI-C A/A) domains total score of 4 or greater. Major exclusion criteria included seizure disorder, delirium, and non-AD dementia.

Interventions: 3 weeks dronabinol vs. placebo titrated up to target dose of 10 mg daily in divided twice-daily.

Main outcomes and measures: Prespecified co-primary agitation outcomes were the Pittsburgh Agitation Scale (PAS) and NPI-C A/A total score.

Results: The majority of participants were female and were taking concomitant psychotropic medications (antidepressants and antipsychotics) at baseline. Study participants were moderately agitated at baseline, were diverse in ethnic background (9% Black, 11% Hispanic/Latina/Latino), and had severe cognitive impairment evidenced by MMSE or SIB-8. 84% completed the 3-week trial.

Dronabinol decreased agitation on both primary outcomes greater than placebo to a clinically relevant extent. The fitted between-arm difference in PAS decline/week was -0.74 (SE 0.3, p = 0.015, effect size = 0.53) and for NPI-C A/A the decline was not significant at -1.26 (SE 0.67, p = 0.094, effect size = 0.36). No secondary outcomes differed between treatment arms including sleep, activities of daily living, Cohen-Mansfield Agitation Inventory (CMAI), cognition, intoxication, or use of ‘as-needed’ lorazepam or trazodone. Dronabinol treatment was not associated with greater intoxication nor with other adverse events (AEs) except for somnolence.

Conclusions and relevance: Adjunctive dronabinol treatment was safe and effective for treating agitation in AD.”

https://pubmed.ncbi.nlm.nih.gov/41350162

“Highlights

•What is the primary question addressed by this study?

Is dronabinol (synthetic THC) a safe and effective treatment for reducing agitation in individuals with Alzheimer’s disease?

•What is the main finding of this study?

In a 3-week randomized, placebo-controlled trial of 75 participants with moderate to severe Alzheimer’s disease, dronabinol significantly reduced agitation as measured by the Pittsburgh Agitation Scale (effect size = 0.53) and showed a trend toward improvement on the NPI-C Agitation/Aggression domain. The medication was well tolerated, with somnolence as the only notable side effect and no increased risk of delirium, falls, or intoxication.

•What is the meaning of the finding?

These results suggest that dronabinol may be a relatively safe and effective pharmacologic option for managing agitation in Alzheimer’s disease.”

https://www.ajgponline.org/article/S1064-7481(25)00506-8/abstract

Cannabinoids in the landscape of cancer

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“Introduction: Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties.

Method: A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types.

Results: Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2.

Conclusion: Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.”

https://pubmed.ncbi.nlm.nih.gov/34259916

“Since time immemorial, the Cannabis plant has been used as a source of fibre, herbal remedy, medicinal and for religious purposes. Plant-based, endogenous and synthetic cannabinoid compounds have shown merits in not only alleviating the unwanted side effects of antineoplastic drug regiments, but have also shown promising evidence in decreasing tumour burden.”

“Plant-based, endogenous and synthetic cannabinoid compounds have shown merits in not only alleviating the unwanted side effects of antineoplastic drug regiments, but have also shown promising evidence in decreasing tumour burden, and one in vivo study so far concludes increasing survival rates in mice.

The antitumour effects of cannabinoids trend in modulating processes which include apoptosis and autophagy through first stimulating de novo synthesis of ceramide which induces activation of ER stress-related signalling proteins further leading to the inhibition of the AKT/mTORC1 axis promoting cell cycle arrest and additional mechanisms, such as cell death and aging.

Other pathways involved mechanistically are activation of MAPK/ERK signalling through calcium induction. Strategies that would optimize the anticancer effects of cannabinoids through interference of these signalling cross-talks may prove useful for therapeutic intervention. Nevertheless, we found that these effects were reached differently downstream depending on the type of cancer, the dosage of the compound and which receptor/ligands were activated.

We also found the co-administration of cannabinoids with chemotherapy drugs enhanced the potency of these effects. These synergistic effects should be targeted for translation to clinical application, especially in cancers which are refractory to chemotherapy.

Various extracted forms of cannabinoids from C. sativa have shown varying cytotoxic effects which should be explored in more detail in future studies as majority of the evidence originates from studies investigating mainly ∆9-THC and CBD’s actions. Whilst the emerging evidence of phytocannabinoid anticancer effects are promising, there remains a paucity of clinical evaluation which must be overcome.”

https://link.springer.com/article/10.1007/s00432-021-03710-7

Plant-derived cannabinoids as anticancer agents

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“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”

https://pubmed.ncbi.nlm.nih.gov/35260379

https://www.cell.com/trends/cancer/abstract/S2405-8033(22)00024-3?