Category Archives: THC (Delta-9-Tetrahydrocannabinol)

The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits

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“Maintaining specific and reproducible cannabinoid compositions (type and quantity) is essential for the production of cannabis-based remedies that are therapeutically effective.

The current study investigates factors that determine the plant’s cannabinoid profile and examines interrelationships between plant features (growth rate, phenology and biomass), inflorescence morphology (size, shape and distribution) and cannabinoid content. An examination of differences in cannabinoid profile within genotypes revealed that across the cultivation facility, cannabinoids’ qualitative traits (ratios between cannabinoid quantities) remain fairly stable, while quantitative traits (the absolute amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV)) can significantly vary.

The calculated broad-sense heritability values imply that cannabinoid composition will have a strong response to selection in comparison to the morphological and phenological traits of the plant and its inflorescences. Moreover, it is proposed that selection in favour of a vigorous growth rate, high-stature plants and wide inflorescences is expected to increase overall cannabinoid production. Finally, a range of physiological and phenological features was utilised for generating a successful model for the prediction of cannabinoid production.

The holistic approach presented in the current study provides a better understanding of the interaction between the key features of the cannabis plant and facilitates the production of advanced plant-based medicinal substances.”

https://pubmed.ncbi.nlm.nih.gov/36771577/

“These findings will have a significant impact on the breeding and cultivation of the chemotypically stable and reproducible cannabis genotypes that will facilitate the production of novel medicinal applications.”

https://www.mdpi.com/2223-7747/12/3/493

Cannabinoids in the Modulation of Oxidative Signaling

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“Cannabis sativa-derived compounds, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and components of the endocannabinoids system, such as N-arachidonoylethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), are extensively studied to investigate their numerous biological effects, including powerful antioxidant effects. Indeed, a series of recent studies have indicated that many disorders are characterized by alterations in the intracellular antioxidant system, which lead to biological macromolecule damage. These pathological conditions are characterized by an unbalanced, and most often increased, reactive oxygen species (ROS) production.

For this study, it was of interest to investigate and recapitulate the antioxidant properties of these natural compounds, for the most part CBD and THC, on the production of ROS and the modulation of the intracellular redox state, with an emphasis on their use in various pathological conditions in which the reduction of ROS can be clinically useful, such as neurodegenerative disorders, inflammatory conditions, autoimmunity, and cancers. The further development of ROS-based fundamental research focused on cannabis sativa-derived compounds could be beneficial for future clinical applications.”

https://pubmed.ncbi.nlm.nih.gov/36768835/

“In conclusion, it has been reported that cannabinoids modulate oxidative stress in inflammation and autoimmunity, which makes them a potential therapeutic approach for different kinds of pathologies.”

https://www.mdpi.com/1422-0067/24/3/2513

Medical cannabis for treatment-resistant combat PTSD

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“Targeting the endocannabinoid system may have a role in the treatment of post-traumatic stress disorder (PTSD). However, few studies have examined the effectiveness of cannabis on symptoms of PTSD, and more research is needed to ascertain cannabis’ effectiveness.

In this retrospective naturalistic study, we followed 14 relatively mature (32-68 years of age), treatment-resistant, chronic combat post-traumatic patients who remained severely symptomatic despite treatment with many lines of conventional treatment prior to receiving medicinal cannabis.

Our findings show that total sleep score, subjective sleep quality, and sleep duration significantly improved (p < 0.01). Total PTSD symptom score and its subdomains (intrusiveness, avoidance, and alertness) showed improvement (p < 0.05). However, there was no improvement in the frequency of nightmares (p = 0.27). The mean follow-up time was 1.1 ± 0.8 years (range of 0.5 to 3 years).”

https://pubmed.ncbi.nlm.nih.gov/36741572/

“To the best of our knowledge, this is the first published study examining long-term cannabis efficacy in chronic combat treatment-resistant PTSD patients. The study we conducted is consistent with existing literature which indicates a decrease in PTSD symptoms under medical cannabis treatment.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1014630/full

Association between cannabis use and blood pressure levels according to comorbidities and socioeconomic status

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Scientific Reports

“The associations between blood pressure and cannabis use remain inconsistent. The purpose of our study was to examine gender stratified associations of cannabis use and blood pressure [systolic, diastolic blood pressure (BP), pulse pressure (PP)] levels among the general UK Biobank population based study. Among 91,161 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low and never users. Associations between cannabis use and BP were estimated using multiple gender linear regressions.

In adjusted covariates models, lifetime heavy cannabis use was associated with decrease in both SBP, DBP and PP in both genders, but with a higher effect among women (for SBP in men, b = − 1.09 (0.27), p < 0.001; in women, b = − 1.85 (0.36), p < 0.001; for DBP in men, b = − 0.50 (0.15), p < 0.001; in women, b = − 0.87 (0.17), p < 0.001; and for PP in men, b = − 0.60 (0.20), p < 0.001; in women, b = − 0.97 (0.27), p < 0.001. Among men, lower SBP and DBP levels were observed with participants without dyslipidemia and lower PP in participants with high income levels. Among women, lower SBP, DBP and PP were observed with current smokers, moderate/low alcohol levels and participants without dyslipidemia.

Current cannabis use was associated with lower SBP levels in men (b = − 0.63 (0.25), p = 0.012) and in women (b = − 1.17 (0.31), p < 0.001). Same results were observed for DBP and PP. Negative association between BP in men was found but not in women. The small association in BP differences between heavy users and never users remains too small to adopt cannabis-blood pressure public policy in clinical practice.”

https://www.nature.com/articles/s41598-022-22841-6

Do tobacco and cannabis use and co-use predict lung function: A longitudinal study

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Respiratory Medicine | Journal | ScienceDirect.com by Elsevier

“Background: Use of tobacco and cannabis is common and has been reported to predict lung function. Less is known about co-use of tobacco and cannabis and their impact on changes in lung function to early adulthood.

Research question: The study examines whether cigarette smoking or cannabis use and co-use are each associated with lung function in a population sample of young adults.

Study design and methods: Data are from a prospective cohort study of cigarette smoking, cannabis use and co-use at 21 and 30 years of age and lung function (FVC, FEV1, FEV1/FVC) measured at 30 years. Lung function results are transformed using Global Lung Function Formulae. Subjects are the children of pregnant women who were recruited into the cohort study over the period 1981-3. Respondents were administered a spirometry assessment at 21 and 30 years of age. These respondents completed a smoking and cannabis use questionnaire at 21- and 30-year follow-ups.

Results: Cigarette smoking (with or without cannabis use) is associated with reduced airflow. There is no consistent association between cannabis use and measures of lung function. The co-use of tobacco and cannabis appears to entail no additional risk to lung function beyond the risks associated with tobacco use alone.

Interpretation: Persistent cigarette smoking is associated with reduced airflow even in young adults. Cannabis use does not appear to be related to lung function even after years of use.”

https://pubmed.ncbi.nlm.nih.gov/36682602/

“•Cigarette smoking and cannabis use and co-use are risk factors for impaired lung function.

•By 30 years, those who have smoked cigarettes since adolescence already show evidence of impairment of lung function.

•By 30 years, those who used cannabis since the adolescent period do not appear to have evidence of impaired lung function.

•Co-use of tobacco and cannabis does not appear to predict lung function beyond the effects of tobacco use alone.”

https://www.resmedjournal.com/article/S0954-6111(23)00012-4/fulltext

“Smoking Cannabis Not Associated With Impaired Lung Functioning In Latest Study”

https://www.forbes.com/sites/emilyearlenbaugh/2023/02/01/smoking-cannabis-not-associated-with-impaired-lung-functioning-in-latest-study/?sh=5f2e60c6a630

State Cannabis Legalization and Psychosis-Related Health Care Utilization

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JAMA editors name the journal's best articles of the decade | American Medical Association

“Importance: Psychosis is a hypothesized consequence of cannabis use. Legalization of cannabis could therefore be associated with an increase in rates of health care utilization for psychosis.

Objective: To evaluate the association of state medical and recreational cannabis laws and commercialization with rates of psychosis-related health care utilization.

Design, setting, and participants: Retrospective cohort design using state-level panel fixed effects to model within-state changes in monthly rates of psychosis-related health care claims as a function of state cannabis policy level, adjusting for time-varying state-level characteristics and state, year, and month fixed effects. Commercial and Medicare Advantage claims data for beneficiaries aged 16 years and older in all 50 US states and the District of Columbia, 2003 to 2017 were used. Data were analyzed from April 2021 to October 2022.

Exposure: State cannabis legalization policies were measured for each state and month based on law type (medical or recreational) and degree of commercialization (presence or absence of retail outlets).

Main outcomes and measures: Outcomes were rates of psychosis-related diagnoses and prescribed antipsychotics.

Results: This study included 63 680 589 beneficiaries followed for 2 015 189 706 person-months. Women accounted for 51.8% of follow-up time with the majority of person-months recorded for those aged 65 years and older (77.3%) and among White beneficiaries (64.6%). Results from fully-adjusted models showed that, compared with no legalization policy, states with legalization policies experienced no statistically significant increase in rates of psychosis-related diagnoses (medical, no retail outlets: rate ratio [RR], 1.13; 95% CI, 0.97-1.36; medical, retail outlets: RR, 1.24; 95% CI, 0.96-1.61; recreational, no retail outlets: RR, 1.38; 95% CI, 0.93-2.04; recreational, retail outlets: RR, 1.39; 95% CI, 0.98-1.97) or prescribed antipsychotics (medical, no retail outlets RR, 1.00; 95% CI, 0.88-1.13; medical, retail outlets: RR, 1.01; 95% CI, 0.87-1.19; recreational, no retail outlets: RR, 1.13; 95% CI, 0.84-1.51; recreational, retail outlets: RR, 1.14; 95% CI, 0.89-1.45). In exploratory secondary analyses, rates of psychosis-related diagnoses increased significantly among men, people aged 55 to 64 years, and Asian beneficiaries in states with recreational policies compared with no policy.

Conclusions and relevance: In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes. As states continue to introduce new cannabis policies, continued evaluation of psychosis as a potential consequence of state cannabis legalization may be informative.”

https://pubmed.ncbi.nlm.nih.gov/36696111/

“In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800728

Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019

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JAMA editors name the journal's best articles of the decade | American Medical Association

“Importance: Patients with chronic pain often receive long-term opioid therapy (LOT), which places them at risk of opioid use disorder and overdose. This presents the need for alternative or companion treatments; however, few studies on the association of medical cannabis (MC) with reducing opioid dosages exist.

Objective: To assess changes in opioid dosages among patients receiving MC for longer duration compared with shorter duration.

Design, setting, and participants: This cohort study of New York State Prescription Monitoring Program data from 2017 to 2019 included patients receiving MC for chronic pain while also receiving opioid treatment. Of these, patients receiving LOT prior to receiving MC were selected. Individuals were studied for 8 months after starting MC. Data were analyzed from November 2021 to February 2022.

Exposures: Selected patients were divided into 2 groups based on the duration of receiving MC: the nonexposure group received MC for 30 days or fewer, and the exposure group received MC for more than 30 days.

Main outcomes and measures: The main outcome was opioid dosage, measured by mean daily morphine milligram equivalent (MME). Analyses were conducted for 3 strata by opioid dosage prior to receiving MC: MME less than 50, MME of 50 to less than 90, and MME of 90 or greater.

Results: A total of 8165 patients were included, with 4041 (median [IQR] age, 57 [47-65] years; 2376 [58.8%] female) in the exposure group and 4124 (median [IQR] age, 54 (44-62) years; 2370 [57.5%] female) in the nonexposure group. Median (IQR) baseline MMEs for the exposure vs nonexposure groups were 30.0 (20.0-40.0) vs 30.0 (20.0-40.0) in the lowest stratum, 60.0 (60.0-70.0) vs 60.0 (60.0-90.0) in the middle stratum, and 150.0 (100.0-216.2) vs 135.0 (100.0-218.0) in the highest stratum. During follow-up, significantly greater reductions in opioid dosage were observed among the exposure group. A dose-response association of patients’ opioid dosage at baseline was observed with the differences in the monthly MME reductions between exposure and nonexposure groups, with a difference of -1.52 (95% CI, -1.67 to -1.37) MME for the lowest stratum, -3.24 (95% CI, -3.61 to -2.87) MME for the middle stratum, and -9.33 (95% CI, -9.89 to -8.77) MME for the highest stratum. The daily MME for the last month of the follow-up period among patients receiving longer MC was reduced by 48% in the lowest stratum, 47% in the middle stratum, and 51% in the highest stratum compared with the baseline dosages. Among individuals in the nonexposure group, daily MME was reduced by only 4% in the lowest stratum, 9% in the middle stratum, and 14% in the highest stratum.

Conclusions and relevance: In this cohort study of patients receiving LOT, receiving MC for a longer duration was associated with reductions in opioid dosages, which may lower their risk of opioid-related morbidity and mortality.”

https://pubmed.ncbi.nlm.nih.gov/36716026/

“This cohort study found that receiving MC for longer was associated with opioid dosage reductions. The reductions were larger among individuals who were prescribed higher dosages of opioids at baseline. These findings contribute robust evidence for clinicians regarding the potential benefits of MC in reducing the opioid burden for patients receiving LOT and possibly reduce their risk for overdose.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800813

“State DOH: Medical cannabis may reduce opioid burden in managing chronic pain”

https://www.troyrecord.com/2023/02/02/state-doh-releases-study-on-role-of-medical-cannabis-for-chronic-pain-reduction/

Inhaled Δ9-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers

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British Journal of Anaesthesia | The Royal College of Anaesthetists

“Background: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined.

Methods: In this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco2 of 55 mm Hg or 7.3 kPa (VE55), measured at 1-h intervals for 7 h after placebo/oxycodone intake.

Results: In 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in VE55, whereas placebo was without effect on VE55. The first cannabis inhalation resulted in VE55 changing from 20.3 (3.1) to 23.8 (2.4) L min-1 (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min-1 (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on VE55, but slightly increased sedation.

Conclusions: In humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment.”

https://pubmed.ncbi.nlm.nih.gov/36725378/

“In pain management, the use of THC or its combination with an opioid can be advantageous, as the combination has an opioid-sparing effect.

However, this is only of advantage provided the combination of these two drug classes does not exacerbate opioid-induced respiratory depression.

In this study, we examined the effect of inhaled medicinal-grade cannabis, containing a high THC dose, on ventilatory control in healthy human volunteers with placebo or oxycodone pretreatment. 

THC has no effect on ventilatory control after placebo or oxycodone pretreatment.

In summary, in human volunteers, THC has no significant effect on ventilatory control after placebo or oxycodone pretreatment.”

https://www.bjanaesthesia.org/article/S0007-0912(22)00743-7/fulltext

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

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SpringerLink

“Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality.

Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis.

However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.”

https://pubmed.ncbi.nlm.nih.gov/36696005/

https://link.springer.com/article/10.1007/s10555-023-10078-2

Molecular insights into the interaction of eighteen different variants of SARS-CoV-2 spike proteins with sixteen therapeutically important phytocompounds: in silico approach

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“SARS-CoV-2 has mutated many times among different populations. We analyzed wild-type spike protein and 18 different variants of SARS-CoV-2 spike protein known until the beginning of 2022 (alpha, beta, B.1.429, B.1.616, B.1.620, B.1.617.3, C.1.2, delta, epsilon, eta, gamma, iota, kappa, lambda, mu, omicron, theta, and zeta) for their interaction with 16 phytocompounds and remdesivir, resulting into 425 combinations. The largest number of mutations has been reported in the omicron followed by delta variant. However, the virulence of the delta variant has been reported higher as compared to omicron. Mutations at a few locations (D215G, K417N, E484K, N501Y, D614G, and P681H) were common in most of the variants.

3 D structures of all the 18 spike proteins were created using SWISS-MODEL to test the binding affinities with caffeine theophylline, emodin, vitexin, berberine, curcumin, piperine, quercetin, artemisinin, carvacrol, capsaicin, tetrahydrocannabinol, cannabidiol, α- pinene, β- pinene and gingerol.

Phytocompounds and mutant variants were prepared using AutoDock 4.2.6 software. Binding affinities of the selected phytocompounds with the different mutant spike proteins were achieved using AutoDock Vina. Out of all combinations investigated, the best binding affinities were observed with 3 variants of SAR-CoV-2 with 5 phytocompounds along with remdesivir. The range of best binding energies varied from -9.1 to -8.0 kcal/mol. Further, MD simulation was done for selected 9 phytocompound-spike mutant complexes for analyzing the stability of interactions for 100 ns.

ADMET studies via ProTox-II and SwissADME displayed that phytocompounds are safe and less toxic in comparison to remdesivir.”

https://pubmed.ncbi.nlm.nih.gov/36690609/

https://www.tandfonline.com/doi/abs/10.1080/07391102.2023.2169761?journalCode=tbsd20