Category Archives: THC (Delta-9-Tetrahydrocannabinol)

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

Efficacy of cannabidiol alone or in combination with Δ-9-tetrahydrocannabinol for the management of substance use disorders: An umbrella review of the evidence

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“Background and aims: Substance use disorders (SUD) lead to a high burden of disease, yet treatment options are limited. Cannabidiol (CBD) is being investigated as a potential therapeutic target due to its pharmacological properties and mode of action in the endocannabinoid system. Recent systematic reviews (SR) on CBD and SUDs have shown inconsistent results. The objective of this umbrella review was to determine whether CBD alone or in combination with Δ-9-tetrahydrocannabinol (THC) is effective for managing and treating SUDs.

Methods: Following a registered protocol, we searched PubMed, Web of Science and Epistemonikos databases for SRs, with or without a meta-analysis, of randomized controlled trials focusing on interventions dispensing CBD, alone or in combination with THC, to treat SUDs, published from 1 January 2000 to 15 October 2024. Screening, data extraction and quality assessment with the AMSTAR 2 tool were performed by two researchers in parallel and duplicated.

Results: 22 SRs were included, 5 of which performed a meta-analysis. We found mixed evidence regarding the efficacy of CBD to manage and treat SUDs. Findings were interpreted in light of the quality of the SRs. Nabiximols, which contains CBD and THC, demonstrated positive effects on cannabis withdrawal and craving symptoms. Evidence supporting the efficacy of CBD is limited and inconclusive for abstinence, reduction or cessation of use of cannabis, tobacco, alcohol, opiates and other psychoactive substances.

Conclusion: Cannabidiol (CBD) monotherapy does not appear to be efficacious for treatment of substance use disorders. CBD primarily exhibits effects on cannabis withdrawal and craving when combined with Δ-9-tetrahydrocannabinol (THC). Existing data on the efficacy of CBD alone with regard to other outcomes related to substance use disorders are limited.”

https://pubmed.ncbi.nlm.nih.gov/39947878/

“This umbrella review does not suggest any efficacy of CBD monotherapy as a therapeutic agent in SUDs. CBD primarily exhibits effects on cannabis withdrawal and craving symptoms when combined with THC in nabiximols. The CBD:THC 1:1 effects suggest that the potential benefits observed in cannabis withdrawal and craving may be because of THC, with CBD providing no additional benefit. We found no evidence for CBD alone, in the absence of THC, in managing cannabis and other SUDs. “

https://onlinelibrary.wiley.com/doi/10.1111/add.16745

Therapeutic potential of cannabinoids in neurological conditions: a systematic review of clinical trials

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“Overview: Cannabinoids have gained increasing attention for their therapeutic potential in treating several neurological conditions, including neurodegenerative diseases, chronic pain, and epilepsy. This review aims to assess the current clinical trials investigating cannabinoids, primarily Tetrahydrocannabinol and Cannabidiol, for neurological disorders. This review will aim to highlight the efficacy, safety, and outcome measures used in these trials.

Methods: Clinical trials were identified using ClinicalTrials.gov, focusing on studies that examined the effects of cannabinoids in treating neurological conditions. All trials that fulfilled the following criteria were included: Phase 1–4, focused on cannabinoids as primary intervention, and measured relevant outcomes such as pain relief, cognitive function, or spasticity reduction. Data on conditions, interventions, primary and secondary outcomes, and trial phases were extracted and analysed.

Results: A total of 47 clinical trials were identified, including different neurological conditions. The most frequently studied conditions were Multiple Sclerosis, Fibromyalgia, and Parkinson’s Disease. Most trials were in Phase 2, with the primary outcome measures focused on pain management, spasticity, and cognitive function. Secondary outcomes included safety and tolerability measures.

Conclusion: The review highlights the broad therapeutic potential of cannabinoids in neurology, with promising results in symptom management for conditions like Multiple Sclerosis and Fibromyalgia. However, the lack of standardized study protocols, dosing, and outcome measures presents challenges for broader clinical implementation.”

“The results of this analysis showed that both CBD and THC have significant potential as therapeutic agents for neurological disorders, particularly in managing pain, motor dysfunction, and behavioural disturbances. However, their different pharmacological profiles and side effect risks mean that each cannabinoid may be better suited to different patient populations and conditions. While THC’s broader range of applications in cognitive and motor symptoms positions it as a more multipurpose treatment option, the psychoactive risks associated with its use should not be ignored. On the other hand, CBD’s safety and non-psychoactive nature make it more preferred option for managing chronic pain, but its therapeutic benefits may be more limited. Future research should focus on addressing the gaps in long-term safety and efficacy data, as well as exploring the full potential of lesser-known cannabinoids and combination therapies to further enhance the treatment of neurological disorders.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1521792/full

Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications

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“A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously.

Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS.

The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders.

Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1G93A mouse model of ALS. The use of CEs in SOD1G93A murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease.

Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.”

https://pubmed.ncbi.nlm.nih.gov/39936266/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28359

Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats

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“Rationale: With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline.

Objectives: The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Methods: Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing.

Results: Acute cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. Chronic oral consumption of Δ9THC enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration.

Conclusions: The results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.”

https://pubmed.ncbi.nlm.nih.gov/39918581/

https://link.springer.com/article/10.1007/s00213-025-06754-6

Acute and prolonged toxicity assessment of Cannabis sativa extract in rodents and lagomorphs

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“Cannabinoids offer a novel pharmacotherapeutic approach and can complement other medications to address unmet clinical needs in numerous patients, which has led to a global increase in the use of these products.

No significant safety concerns have been identified in preclinical studies involving CBD and THC. However, the available data on the toxicity of combined CBD and THC are still inconclusive. Evaluating full-spectrum Cannabis sativa extracts is even more complex since whole extracts and isolated phytomolecules do not act in the same way.

Given the growing interest in cannabinoid-containing products for human use and the fact that most cannabis treatments utilize entire inflorescence rather than isolated compounds, the current studies aim to evaluate the preclinical safety of a full-spectrum composition (THC, CBD, minor cannabinoids, terpenes, and flavonoids) Cannabis sativa extract (CSE).

This research includes acute (single dose, with animals monitored for 14 days to assess potential effects) and long-term treatments (6 months for rodents and 9 months for rabbits) to assess safety and tolerance.

This study demonstrates that a full-spectrum Cannabis sativa extract has a favorable safety profile in both acute and prolonged toxicity studies in rodents and rabbits.

In acute toxicity tests, the extract did not show any significant behavioral or physiological changes after oral or intraperitoneal administration. Additionally, administering the extract acutely to rabbits had minimal impact on the central nervous, cardiovascular, and respiratory systems, with only a temporary reduction in motor activity at the highest dose.

Prolonged administration of 6 months in rats and 9 months in rabbits did not lead to significant changes in organ histopathology, body weight, or behavior.

Although liver enzymes were elevated at the highest doses, other biochemical and hematological parameters remained unchanged. CSE was well-tolerated, as no serious adverse effects were observed; however, a reduction in motor activity was noted in the highest dose group, highlighting the need for further investigation, which is proposed for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39917037/

https://www.sciencedirect.com/science/article/pii/S2214750025000368?via%3Dihub

Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

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“The medicinal and recreational uses of Cannabis sativa have been recognized for thousands of years.

Today, cannabis-derived medicines are used to treat a variety of conditions, including chronic pain, epilepsy, multiple sclerosis, and chemotherapy-induced nausea. However, cannabis use disorder (CUD) has become the third most prevalent substance use disorder globally.

Cannabinoid receptors are the primary targets that mediate the effects of cannabis and its analogs. Despite their importance, the mechanisms of modulation and the full therapeutic potential of cannabinoid receptors remain unclear, hindering the development of the next generation of cannabinoid-based drugs.

This review summarizes the discovery and medicinal potential of phytocannabinoids and explores the distribution, signaling pathways, and functional roles of cannabinoid receptors. It also discusses classical cannabinoid drugs, as well as agonists, antagonists, and inverse agonists, which serve as key therapeutic agents.

Recent advancements in the development of allosteric drugs are highlighted, with a focus on positive and negative allosteric modulators (PAMs and NAMs) that target CB1 and CB2 receptors. The identification of multiple allosteric sites on the CB1 receptor and the structural basis for allosteric modulation are emphasized, along with the structure-based discovery of ago-BAMs for CB1.

This review concludes by examining the future potential of allosteric modulators in cannabinoid drug development, noting that ongoing progress in cannabinoid-derived drugs continues to open new avenues for therapeutic use and paves the way for future research into their full medicinal potential.”

https://pubmed.ncbi.nlm.nih.gov/39910211/

https://www.nature.com/articles/s41401-024-01472-9

The effects of recreational cannabis laws on alcohol and tobacco use among US adults, 2012 to 2022

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“Introduction: Many states have legalized cannabis for medicinal and recreational purposes in the past decade. However, it is unclear how recreational cannabis laws (RCLs) may affect alcohol and tobacco use among adults.

Methods: This is a cross-sectional study of 4.8 million adults from the 2012-2022 Behavioral Risk Factor Surveillance System. A difference-in-differences approach was used to examine the impact of RCLs on the use of alcohol and tobacco, adjusting for individual-level characteristics and time-varying state-level factors. The analyses were performed in 2024.

Results: Three alcohol use outcomes (current drinking, binge drinking, and heavy drinking) and two tobacco use outcomes (current tobacco use and smokeless tobacco use) were examined. Considering passage of cannabis laws as RCL implementation,

RCLs were not associated with any alcohol or tobacco use outcomes in the fully adjusted model. However, considering operational dispensary as RCL implementation, RCLs were associated with a decrease of 0.95 percentage point (95% CI, 1.80 to 0.09) in current drinking and a decrease of 0.48 percentage point (95% CI, 0.85 to 0.10) in current cigarette use.

Subgroup analysis showed that RCLs were associated with reductions in current drinking, binge drinking, and current cigarette use in multiple groups. However, RCLs were associated with increases in current smokeless tobacco use for some groups.

Conclusions: The findings suggest that while the overall effects of RCLs on the use of alcohol and tobacco may be limited, there are heterogeneous associations of RCLs with drinking and smoking by age, sex, race and ethnicity, education, and income.”

https://pubmed.ncbi.nlm.nih.gov/39909135/

https://www.ajpmonline.org/article/S0749-3797(25)00038-8/abstract