Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial

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“Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was 1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization.

Results Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events.

Conclusions Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.”

https://pubmed.ncbi.nlm.nih.gov/38405890/

https://www.medrxiv.org/content/10.1101/2024.02.16.24302843v1

Therapeutic Potential of Cannabinoid Profiles Identified in Cannabis L. Crops in Peru

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“Cannabis is a plant that is cultivated worldwide, and its use is internationally regulated, but some countries have been regulating its medicinal, social, and industrial uses. This plant must have arrived in Peru during the Spanish conquest and remains widely cultivated illicitly or informally to this day. However, new regulations are currently being proposed to allow its legal commercialization for medicinal purposes.

Cannabis contains specific metabolites known as cannabinoids, some of which have clinically demonstrated therapeutic effects. It is now possible to quantitatively measure the presence of these cannabinoids in dried inflorescences, thus allowing for description of the chemical profile or “chemotype” of cannabinoids in each sample.

This study analyzed the chemotypes of eight samples of dried inflorescences from cannabis cultivars in four different regions of Peru, and based on the significant variation in the cannabinoid profiles, we suggest their therapeutic potential.

The most important medical areas in which they could be used include the following: they can help manage chronic pain, they have antiemetic, anti-inflammatory, and antipruritic properties, are beneficial in treating duodenal ulcers, can be used in bronchodilators, in muscle relaxants, and in treating refractory epilepsy, have anxiolytic properties, reduce sebum, are effective on Methicillin-resistant Staphylococcus aureus, are proapoptotic in breast cancer, can be used to treat addiction and psychosis, and are effective on MRSA, in controlling psoriasis, and in treating glioblastoma, according to the properties of their concentrations of cannabidiol, cannabigerol, and Δ9-tetrahydrocannabinol, as reviewed in the literature. On the other hand, having obtained concentrations of THC, we were able to suggest the psychotropic capacity of said samples, one of which even fits within the legal category of “non-psychoactive cannabis” according to Peruvian regulations.”

https://pubmed.ncbi.nlm.nih.gov/38397908/

https://www.mdpi.com/2227-9059/12/2/306

Unveiling the Potential of Cannabinoids in Multiple Sclerosis and the Dawn of Nano-Cannabinoid Medicine

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“Multiple sclerosis is the predominant autoimmune disorder affecting the central nervous system in adolescents and adults. Specific treatments are categorized as disease-modifying, whereas others are symptomatic treatments to alleviate painful symptoms.

Currently, no singular conventional therapy is universally effective for all patients across all stages of the illness. Nevertheless, cannabinoids exhibit significant promise in their capacity for neuroprotection, anti-inflammation, and immunosuppression.

This review will examine the traditional treatment for multiple sclerosis, the increasing interest in using cannabis as a treatment method, its role in protecting the nervous system and regulating the immune system, commercially available therapeutic cannabinoids, and the emerging use of cannabis in nanomedicine.

In conclusion, cannabinoids exhibit potential as a disease-modifying treatment rather than merely symptomatic relief. However, further research is necessary to unveil their role and establish the safety and advancements in nano-cannabinoid medicine, offering the potential for reduced toxicity and fewer adverse effects, thereby maximizing the benefits of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/38399295/

https://www.mdpi.com/1999-4923/16/2/241

Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66

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“Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells.

Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated.

This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis.

The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels.

These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38334660/

https://www.mdpi.com/2073-4409/13/3/268

Removing barriers to accessing medical cannabis for paediatric patients

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“Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.”

https://pubmed.ncbi.nlm.nih.gov/38332979/

https://academic.oup.com/pch/article/29/1/12/7098192?login=false

Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome

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“This randomized controlled crossover trial examined the use of oral tetrahydrocannabinol (THC) with cannabidiol (CBD) to reduce tics in patients with severe Tourette syndrome. Treatment with THC and CBD for 6 weeks led to a significant reduction in tics as measured by the total tic score on the Yale Global Tic Severity Scale, without major adverse effects.”

https://pubmed.ncbi.nlm.nih.gov/38320199/

“BACKGROUND

Tourette syndrome is characterized by chronic motor and vocal tics. There is preliminary evidence of benefit from cannabis products containing Δ9-tetrahydrocannabinol (THC) and that coadministration of cannabidiol (CBD) improves the side-effect profile and safety.

METHODS

In this double-blind, crossover trial, participants with severe Tourette syndrome were randomly assigned to a 6-week treatment period with escalating doses of an oral oil containing 5 mg/ml of THC and 5 mg/ml of CBD, followed by a 6-week course of placebo, or vice versa, separated by a 4-week washout period. The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0 to 50 [higher scores indicate greater severity of symptoms]). Secondary outcomes included video-based assessment of tics, global impairment, anxiety, depression, and obsessive-compulsive symptoms. Outcomes were correlated with plasma levels of cannabinoid metabolites. A computerized cognitive battery was administered at the beginning and the end of each treatment period.

RESULTS

Overall, 22 participants (eight female participants) were enrolled. Reduction in total tic score (at week 6 relative to baseline) as measured by the YGTSS was 8.9 (±7.6) in the active group and 2.5 (±8.5) in the placebo group. In a linear mixed-effects model, there was a significant interaction of treatment (active/placebo) and visit number on tic score (coefficient = −2.28; 95% confidence interval, −3.96 to −0.60; P=0.008), indicating a greater decrease (improvement) in tics under active treatment. There was a correlation between plasma 11-carboxy-tetrahydrocannabinol levels and the primary outcome, which was attenuated after exclusion of an outlier. The most common adverse effect in the placebo period was headache (n=7); in the active treatment period, it was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration (n=8).

CONCLUSIONS

In severe Tourette syndrome, treatment with THC and CBD reduced tics and may reduce impairment due to tics, anxiety, and obsessive-compulsive disorder; although in some participants this was associated with slowed mentation, memory lapses, and poor concentration.”

https://evidence.nejm.org/doi/10.1056/EVIDoa2300012

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® – A Cannabis-derived Spray

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“Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants.

Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders.

The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.”

https://pubmed.ncbi.nlm.nih.gov/38318827/

https://www.eurekaselect.com/article/138318

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression

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“Introduction: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes.

Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure.

Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds.

Methods: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α).

Results: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed.

Conclusions: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.”

https://pubmed.ncbi.nlm.nih.gov/38320364/

https://www.journalofsurgicalresearch.com/article/S0022-4804(24)00037-4/fulltext

Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

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“Introduction: Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction (‘F7’) and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3. 

Materials and methods: Gene expression profiles were determined by RNA sequencing and quantitative PCR. Microscopy was used to determine actin arrangement, a scratch assay to determine cell migration and flow cytometry to determine apoptosis, cell cycle and aldehyde dehydrogenase (ALDH) activity. Western blotting was used to determine protein levels. 

Results: Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-β/Activin and MAPK were enriched with genes differentially expressed by niraparib and/or F7 treatments in both cell lines. Niraparib + F7 treatment led to cell cycle arrest and endoplasmic reticulum (ER) stress, inhibited cell migration, reduced the % of ALDH positive cells in the population and enhanced PARP1 cleavage. 

Conclusion: The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.”

https://pubmed.ncbi.nlm.nih.gov/38322025/

“Cannabis sativa is utilized worldwide for palliative care and to alleviate various symptoms associated with medical conditions. Several dozen compounds are biosynthesized in the female inflorescence of each C. sativa strain. In total, around 600 different molecules can be found in cannabis, among them around 150 phytocannabinoids and hundreds of flavonoids and terpenes

Multiple studies suggest that phytocannabinoids have anti-cancer properties.

They inhibit several different features associated with cancer cells and tumors, including inhibiting cell proliferation and migration, inducing cell death, reducing angiogenesis, and inhibiting cancer cells’ invasiveness. This was demonstrated in several different cancer types, including cancers of the skin, lung, breast, prostate, and brain.

The best-studied anti-cancer activity is that of the most common phytocannabinoids cannabidiol (CBD) and Δ9–tetrahydrocannabinol (THC), and related synthetic compounds (e.g., HU-210 and WIN-55 212-2).

Phytocannabinoids have been found to affect cancer cells and tumors via several different genetic pathways and molecular mechanisms. For example, several signal transduction pathways can be activated by phytocannabinoids to induce cancer cell death, including cell cycle arrest, endoplasmic reticulum (ER) stress, oxidative stress, autophagy and/or apoptosis.”

https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1333964/full


Antiviral Activities of Cannabis

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“Despite the history of scientific evidence regarding plants and their products in prophylactics and therapeutics, their applications in healthcare systems are only now gaining momentum.

Plants contain bioactive compounds that target certain viruses to cure or prevent viral diseases and infections.

They provide a rich resource of antiviral drugs. Identifying the antiviral mechanisms in plants has shed light on where they interact with the life cycle of viruses, such as viral entry, replication, assembly, and release.”

https://link.springer.com/chapter/10.1007/978-3-031-35155-6_13