Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

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“Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of the cannabinoid 1 (CB1) receptor, part of the endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), a non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in a murine model of dextran sodium sulphate (DSS)-induced colitis. 

Methods: Acute colitis was induced with 4% DSS for 7 days, followed by 3 days of water. Chronic colitis was modelled over 24 days with alternating DSS concentrations. The combination of 2.5 mg/kg THC with 20 mg/kg ZCZ011 or 10 mg/kg CBD was evaluated. Key markers were assessed to determine efficacy and safety, including disease activity index (DAI), inflammation, cytokine levels, GLP-1, and organ health. 

Results: DSS-induced colitis resulted in increased DAI scores, cytokines, organ inflammation and dysregulation of GLP-1 and ammonia. THC at 10 mg/kg significantly improved colitis markers but was ineffective at 2.5 and 5 mg/kg. ZCZ011 alone showed transient effects. However, combining 2.5 mg/kg THC with either 20 mg/kg ZCZ011 or 10 mg/kg CBD significantly alleviated colitis markers, restored colon integrity and reestablished GLP-1 homeostasis. This combination also maintained favourable haematological and biochemical profiles, including a notable reduction in colitis-induced elevated ammonia levels. 

Conclusions: This study demonstrates the synergistic potential of low-dose THC combined with CBD or ZCZ011 as a novel, effective and safer therapeutic strategy for ulcerative colitis.”

https://pubmed.ncbi.nlm.nih.gov/40005963/

“This study provides compelling evidence that sub-therapeutic doses of THC combined with ZCZ011 or CBD offer a safe and effective strategy for managing both the inflammatory and metabolic components of IBD. Notably, the normalisation of GLP-1 and ammonia levels underscores the dual benefits of these treatments in alleviating colitis while addressing associated metabolic dysregulation and extraintestinal complications. This dual-action approach addresses key limitations of current therapies and emphasizes ECS modulation as a promising avenue for IBD treatment.”

https://www.mdpi.com/1424-8247/18/2/148

Modulation of the endocannabinoid system in chronic conditions: a potential therapeutic intervention yet to be explored in sickle cell disease

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“Introduction: Individuals living with Sickle Cell Disease (SCD) are subject to numerous chronic complications, including disabling chronic pain, often dependent on opioids and with important repercussions on quality of life. The use of Medicinal Cannabis in this scenario may be a promising strategy for mitigating this impact.

Areas covered: This work compiled current knowledge regarding the endocannabinoid system in humans and the role of this system in various organic functions. Articles were retrieved through a comprehensive search of the PubMed NCBI database, covering relevant studies up to 2024. These data bring important speculations on the potential role of the use of medicinal cannabis in modulating SCD chronic complications, and the preliminary results of clinical trials carried out in this condition are discussed.

Expert opinion: The search for understanding the role of cannabis-derived products in the management of chronic complications of sickle cell disease could add resources to the serious challenge of dealing with the multiple aspects of the disease faced by patients. They range from the management of chronic pain itself, the risks of opioid dependence, in addition to other difficult scenarios, such as leg ulcers and chronic inflammation and its consequences.”

https://pubmed.ncbi.nlm.nih.gov/39992131/

https://www.tandfonline.com/doi/full/10.1080/17474086.2025.2471864

Combined effects of cannabidiol and Δ9-tetrahydrocannabinol alleviate migraine-like symptoms in mice

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“Background: The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).

Methods: Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).

Results: In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.

Conclusions: A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.”

https://pubmed.ncbi.nlm.nih.gov/39988876/

“Our preclinical findings suggest that cannabinoids may have therapeutic potential for treating migraine symptoms without causing adverse effects. These findings are in line with previous studies that have suggested that cannabinoids may be effective in treating pain and migraine.”

https://journals.sagepub.com/doi/10.1177/03331024251314487

Cannabis Use in HIV: Impact on Inflammation, Immunity and the Microbiome

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“Purpose of review: This review explores how cannabis impacts the gut microbiome, immune system, and ART outcomes in people with HIV (PWH). Given the increasing prevalence of cannabis use among PWH, we investigated its potential to reduce chronic inflammation and enhance gut health, both of which can influence HIV pathogenesis.

Recent findings: Cannabis has immunomodulatory and anti-inflammatory effects, including reducing systemic inflammatory biomarkers (such as MCP-1 and IP-10) and improving gut barrier integrity through increased short-chain fatty acid (SCFA) production.

Studies have shown that cannabis use is associated with increased gut mucosal immunity, decreased immune activation, and a unique microbiome composition. Preliminary evidence indicates that cannabis may influence HIV reservoirs, although the results remain inconclusive.

Cannabis shows promise in managing inflammation, gut dysbiosis, and immune dysfunction in PWH. However, its effects on HIV reservoirs, adherence to antiretroviral therapy, and long-term outcomes need further investigation through rigorous clinical trials using standardized formulations.”

https://pubmed.ncbi.nlm.nih.gov/39984806/

https://link.springer.com/article/10.1007/s11904-025-00729-0

Impacts of vaping and marijuana use on airway health as determined by exhaled breath condensate (EBC)

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“Across the United States, there is increased use of cannabis products and electronic delivery systems for cannabis products and nicotine, yet little is known about their impacts on lung health.

We analyzed exhaled breath condensate of 254 participants who were non-users and users who used cannabis and tobacco products. The 132 participants reported using a product (“users”) were distributed into cohorts of tobacco products and cannabis products, with some participants following into multiple cohorts.

Targeted analysis of inflammatory oxylipins found up-regulation among persons using tobacco products, while cannabis users had concentrations closer to nonusers, and often down-regulated.

Untargeted screening of 403 significant metabolites found tobacco users had similar breath profiles, and that cannabis users had a similar profile that was closer to the profile of nonusers.

Metabolites were significantly higher in breath of people using combustion products (tobacco and cannabis) relative to nonusers, and significantly lower in e-device users (nicotine and THC). Our work demonstrates the relative impact of e-delivery systems and cannabis products compared to traditional cigarette smoking on lung metabolic profiles.”

https://pubmed.ncbi.nlm.nih.gov/39984952/

“Analysis of exhaled breath condensate was used to compare human metabolomic information of persons using tobacco and cannabis related products. Targeted measurements of oxylipin inflammatory markers found significant up-regulation among those using tobacco products relative to nonusers.

Cannabis users exhibited oxylipin levels closer to and often downregulated compared to nonusers. However, direct links to clinical outcomes such as lung disease or respiratory dysfunction were not established, limiting conclusions about the clinical impact of these biomarkers.

Untargeted screening of breath metabolites found that users of cigarettes, nicotine vapes, and any tobacco product had similar metabolite profiles, whereas cannabis smokers, vapers, and product users had a profile that was more similar to nonusers.”

https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03147-3


Effectiveness of a Cannabinoids Supplement on Sleep and Mood in Adults With Subthreshold Insomnia: A Randomized Double-Blind Placebo-Controlled Crossover Pilot Trial

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“Background and aims: Conduct a pilot randomized double-blind placebo-controlled crossover trial for adults with subthreshold insomnia symptoms to examine the effectiveness of a cannabinoids supplement on sleep quality and health outcomes.

Methods: Adults with subthreshold insomnia symptoms (N = 20, Mage = 47.40) were randomized to either the Cannabinoids Supplement (CS) or Placebo Condition (PC) for 10 days. The CS was an oral soft gel that contained 3 mg Δ9-tetrahydrocannabinol, 6 mg cannabinol, 10 mg cannabidiol, and 90 mg of a proprietary food-grade terpene blend. Following a 2-week washout, they completed the alternate condition. The following validated questionnaires were collected at baseline and following each condition: Insomnia Severity Index, Pittsburgh Sleep Quality Index, Bergen Insomnia Scale, Profile of Mood States (POMS), Perceived Stress Scale, Pain and Sleep Questionnaire. Trait Anxiety Inventory, Flinders Daytime Fatigue, and Health-related Quality of Life Scale. Clinical trial registry number = ISRCTN 15022302.

Results: When compared to PC, the CS Condition had significantly improved sleep quality/efficiency, insomnia symptoms, and health-related quality of life, p < 0.05. Nonsignificant improvements for the CS compared to the PC were found for the POMS mood subscales of tension, anger, fatigue, depression, and vigor, as well as anxiety. The Esteem subscale improved significantly from Baseline to Post for the PC. Both the CS and PC Vigor improved significantly from baseline. Anxiety improved significantly from Baseline to Post for the CS. No adverse events reported.

Conclusion: This cannabinoid-based formulation was a well-tolerated oral supplement that may improve adults’ sleep quality/efficiency and health-related quality of life. Larger controlled trials are encouraged to examine the longer-term effects of this supplement in a variety of populations and environments.”

https://pubmed.ncbi.nlm.nih.gov/39980821/

https://onlinelibrary.wiley.com/doi/10.1002/hsr2.70481

Medical Cannabis for Patients Over Age 50: A Multi-site, Prospective Study of Patterns of Use and Health Outcomes

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“Objective: Cannabis is being used as a therapeutic option by patients around the globe, and older patients represent a rapidly growing subset of this population. This study aims to assess the patterns of medical cannabis use in patients over 50 years of age and its effect on health outcomes such as pain, sleep, quality of life, and co-medication.

Method: The Medical Cannabis in Older Patients Study (MCOPS) is a multi-site, prospective observational study examining the real-world impact of medical cannabis use on patients over age 50 under the guidance of a health care provider. The study included validated instruments, with treating physicians collecting detailed data on participant characteristics, medical cannabis and co-medication use, and associated impacts on pain, sleep, quality of life, as well as adverse events.

Results: Inclusion criteria were met by 299 participants. Average age of participants was 66.7 years, and 66.2% of respondents identified as female. Approximately 90% of patients used medical cannabis to treat pain-related conditions such as chronic pain and arthritis. Almost all patients reported a preference for oral cannabis products (e.g., extracts, edibles) rather than inhalation products (e.g., flower, vapes), and most preferred oral formulations high in cannabidiol and low in tetrahydrocannabinol.

Over the six-month study period, significant improvements were noted in pain, sleep, and quality of life measures, with 45% experiencing a clinically meaningful improvement in pain interference and in sleep quality scores. Additionally, nearly 50% of patients taking co-medications at baseline had reduced their use by the end of the study period, and quality of life improved significantly from baseline to M3 and from baseline to M6, with an incremental cost per quality-adjusted life-year (QALY) of $25,357.20. No serious adverse events (SAEs) were reported.

Conclusions: In this cohort of older patients, most of whom suffered from pain-related conditions, medical cannabis seemed to be a safe and effective treatment. Most patients experienced clinically significant improvements in pain, sleep, and quality of life and reductions in co-medication. The cost per QALY was well below the standard for traditional pharmaceuticals, and no SAEs were reported, suggesting that cannabis is a relatively safe and cost-effective therapeutic option for adults dealing with age-related health conditions.”

https://pubmed.ncbi.nlm.nih.gov/39968489/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/239

Recreational Cannabis Laws and Fills of Pain Prescriptions in the Privately Insured

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“Objective: Almost half of U.S. states have passed recreational cannabis laws as of May 2024. While considerable evidence to date indicates cannabis may be a substitute for prescription opioids in the treatment of pain, it remains unclear if patients are treating pain with cannabis alone or concomitantly with other medications.

Method: Using data from a national sample of commercially insured adults, we examine the effect of recreational cannabis legalization (through two sequential policies) on prescribing of opioids, NSAIDS, and other pain medications by implementing synthetic control estimations and constructing case-study level counterfactuals for the years 2007-2020.

Results: Overall, we find recreational cannabis legalization is associated with a decrease in opioid fills among commercially insured adults in the U.S., and we find evidence of a compositional change in prescriptions of pain medications more broadly. Specifically, we find marginally significant increases in prescribing of non-opioid pain medications after recreational cannabis becomes legal in some states. Once recreational cannabis dispensaries open, we find statistically significant decreases in the rate of opioid prescriptions (13% reduction from baseline, p < .05) and marginally significant decreases in the average daily supply of opioids (6.3% decrease, p < .10) and number of opioid prescriptions per patient (3.5% decrease, p < .10).

Conclusions: These results suggest that substitution of cannabis for traditional pain medications increases as the availability of recreational cannabis increases. There appears to be a small shift once recreational cannabis becomes legal, but we see stronger results once users can purchase cannabis at recreational dispensaries. The decrease in opioids and marginal increase in non-opioid pain medication may reflect patients substituting opioids with cannabis and non-opioid pain medications, either separately or concomitantly. Reductions in opioid prescription fills stemming from recreational cannabis legalization may prevent exposure to opioids in patients with pain and lead to decreases in the number of new opioid users, rates of opioid use disorder, and related harms.”

https://pubmed.ncbi.nlm.nih.gov/39968486/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/268

Motherhood and medicinal cannabis

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“Introduction: Women are emerging as a key demographic for medicinal cannabis (MC) use in countries that have implemented MC reforms. However, research on mothers’ experiences of consuming MC remains limited beyond studies on perinatal outcomes. This study explores mothers’ diverse experiences of consuming MC in New Zealand under the legal MC scheme.

Methods: Interviews with 15 mothers using MC via prescriptions, the illegal market or both in the last 12 months. Thematic analysis focused on MC use in parenting, MC conversations with children, societal stigma and risks.

Results: Mothers reported MC as an important facilitator of their ability to positively parent their children, enabling them to manage their own health needs (i.e., anxiety, endometriosis and arthritis). High costs of legal products hindered access to MC. Participants expressed unique risks that mothers face accessing the unregulated market for MC like being deemed a ‘bad mother’ and losing custody of children. Stigma was countered with narratives of empowerment through proactive MC conversations with children and agency by self-medicating with MC despite the judgement they may face for being a parent that uses cannabis.

Discussion and conclusions: Mothers felt managing their health with MC allowed them to be more present parents and better tolerate the stressors of motherhood. In-depth exploration of discussing MC with children and anticipating these conversations was a novel finding. Most mothers tried to destigmatise MC in conversations by classifying it in the same category as other medications and discussing its therapeutic benefits. Few were cautious about having these conversations too early.”

https://pubmed.ncbi.nlm.nih.gov/39967064/

“This study has provided insights into MC use among mothers, highlighting perceived therapeutic benefits for managing the unique stressors of motherhood and health and wellbeing in general. The findings illustrate the global legalisation of MC as a possible catalyst for shifting attitudes towards cannabis use in parenting, and a trend of women exercising agency in their health using complementary alternative therapies.”

https://onlinelibrary.wiley.com/doi/10.1111/dar.14027

THC shows activity against cultured Plasmodium falciparum

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“The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites.

The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa.

Traditional use of cannabis for malaria fever was reported in the world’s oldest pharmacopoeia, dating to around 5000 years ago.

In this research we report that THC inhibits β-haematin (synthetic haemozoin) and malaria parasite growth.

Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited β-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action.

For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.”

https://pubmed.ncbi.nlm.nih.gov/34763083/

https://www.sciencedirect.com/science/article/abs/pii/S0960894X21006697?via%3Dihub