Tag Archives: THC

Joints for joints: cannabinoids in the treatment of rheumatoid arthritis.

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“An increasing number of patients with rheumatoid arthritis (RA) are using cannabis to treat their symptoms, although systematic studies regarding efficacy in RA are lacking. Within this review we will give an overview on the overall effects of cannabinoids in inflammation and why they might be useful in the treatment of RA.

RECENT FINDINGS:

Peripherally, cannabinoids show anti-inflammatory effects by activating cannabinoid type 2 receptors (CB2) which decrease cytokine production and immune cell mobilization. In contrast, cannabinoid type 1 receptor (CB1) activation on immune cells is proinflammatory while CB1 antagonism provides anti-inflammatory effects by increasing β2-adrenergic signaling in the joint and secondary lymphoid organs. In addition, the nonpsychotropic cannabinoid, cannabidiol (CBD) demonstrated antiarthritic effects independent of cannabinoid receptors. In addition to controlling inflammation, cannabinoids reduce pain by activating central and peripheral CB1, peripheral CB2 receptors and CBD-sensitive noncannabinoid receptor targets.

SUMMARY:

Cannabinoids might be a suitable treatment for RA, but it is important to target the right receptors in the right place. For clinical studies, we propose a combination of a CB2 agonist to decrease cytokine production, a peripheral CB1 antagonist to prevent detrimental CB1 signaling and to support anti-inflammatory effects of CB2 via activation of β2-adrenergic receptors and CBD to induce cannabinoid-receptor-independent anti-inflammatory effects.”

 https://www.ncbi.nlm.nih.gov/pubmed/30920973
https://insights.ovid.com/crossref?an=00002281-201905000-00009

Bronchodilator effect of delta1-tetrahydrocannabinol.

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“1 delta1-trans-tetrahydrocannabinol, (delta1-THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). 3 The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.”

https://www.ncbi.nlm.nih.gov/pubmed/656294

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1429361/

“Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics.” https://www.ncbi.nlm.nih.gov/pubmed/797044

“Bronchodilators are medications that open (dilate) the airways (bronchial tubes) of the lung by relaxing bronchial muscles and allow people who have difficulty breathing to breath better. Bronchodilators are used for treating:

https://www.medicinenet.com/bronchodilators_for_asthma/article.htm

Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies.

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 Image result for journal of central nervous system disease“Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability.

Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies.

METHODS:

A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria.

RESULTS:

In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice.

CONCLUSIONS:

The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.”

https://www.ncbi.nlm.nih.gov/pubmed/30886530

https://journals.sagepub.com/doi/10.1177/1179573519831997

Beneficial and deleterious effects of cannabinoids in the brain: the case of ultra-low dose THC.

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“This article reviews the neurocognitive advantages and drawbacks of cannabinoid substances, and discusses the possible physiological mechanisms that underlie their dual activity. The article further reviews the neurocognitive effects of ultra-low doses of ∆9-tetrahydrocannabinol (THC; 3-4 orders of magnitude lower than the conventional doses) in mice, and proposes such low doses of THC as a possible remedy for various brain injuries and for the treatment of age-related cognitive decline.”

https://www.ncbi.nlm.nih.gov/pubmed/30864864

https://www.tandfonline.com/doi/abs/10.1080/00952990.2019.1578366?journalCode=iada20

Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit.

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“Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients’ perceived benefit of cannabinoids for Gp symptoms.

METHODS:

Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments.

RESULTS:

Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use.

CONCLUSIONS:

A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.”

https://www.ncbi.nlm.nih.gov/pubmed/30865015

https://journals.lww.com/ajg/Abstract/2019/06000/Cannabinoid_Use_in_Patients_With_Gastroparesis_and.23.aspx

Promoting cannabis products to pharmaceutical drugs.

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European Journal of Pharmaceutical Sciences

“Cannabis sativa is widely used for medical purposes. However, to date, aroma, popular strain name or the content of two phytocannabinoids-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are mostly considered for therapeutic activity. This is despite the hundreds of compounds in this plant and their potential synergistic interactions in mixtures. New, specific and effective cannabis-based drugs must be developed to achieve adequate medical standards for the use of cannabis. To do this, the comprehensive molecular profile of cannabis-based drugs must be defined, and mixtures of compounds should be tested for superior therapeutic activity due to synergistic effects compared to individually isolated cannabis compounds. The biological pathways targeted by these new drugs should also be characterized more accurately. For drug development and design, absorption, distribution, metabolism and elimination versus toxicity (ADME/Tox) must be characterized, and therapeutic doses identified. Promoting the quality and therapeutic activity of herbal or synthetic cannabis products to pharma grade is a pressing need worldwide.”

https://www.ncbi.nlm.nih.gov/pubmed/30851400

https://www.sciencedirect.com/science/article/pii/S0928098719300880?via%3Dihub

The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder.

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 Related image“Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs’ therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD’s promise, further investigation and validation of CBD’s efficacy, across preclinical and clinical trials will be necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/30837904

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00063/full

Association Between Cannabis Use and Complications Related to Crohn’s Disease: A Retrospective Cohort Study.

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“Crohn’s disease is an idiopathic inflammatory process that is occasionally associated with complications, which cause significant morbidity and mortality. The anti-inflammatory effect of cannabis in intestinal inflammation has been shown in several experimental models; it is unknown whether this correlates with fewer complications in Crohn’s disease patients.

AIMS:

To compare the prevalence of Crohn’s disease-related complications among cannabis users and non-users in patients admitted with a primary diagnosis of Crohn’s disease or a primary diagnosis of Crohn’s related complication and a secondary diagnosis of Crohn’s disease between 2012 and 2014.

METHODS:

We used data from the Healthcare Cost and Utilization Project-National Inpatient Sample. Cannabis users (615) were compared directly after propensity score match to non-users, in aspects of various complications and clinical end-points.

RESULTS:

Among matched cohorts, Cannabis users were less likely to have the following: active fistulizing disease and intra-abdominal abscess (11.5% vs. 15.9%; aOR 0.68 [0.49 to 0.94], p = 0.025), blood product transfusion (5.0% vs. 8.0%; aOR 0.48 [0.30 to 0.79], p = 0.037), colectomy (3.7% vs. 7.5%; aOR 0.48 [0.29-0.80], p = 0.004), and parenteral nutrition requirement (3.4% vs. 6.7%, aOR 0.39 [0.23 to 0.68], p = 0.009).

CONCLUSION:

Cannabis use may mitigate several of the well-described complications of Crohn’s disease among hospital inpatients. These effects could possibly be through the effect of cannabis in the endocannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/30825109

https://link.springer.com/article/10.1007%2Fs10620-019-05556-z

Acute effect of vaporized Cannabis on sleep and electrocortical activity.

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Pharmacology Biochemistry and Behavior

“The use of Cannabis for medical purposes is rapidly expanding and is usually employed as a self-medication for the treatment of insomnia disorder.

However, the effect on sleep seems to depend on multiple factors such as composition of the Cannabis, dosage and route of administration. Vaporization is the recommended route for the administration of Cannabis for medical purposes; however, there is no published research about the effects of vaporized Cannabis on sleep, neither in laboratory animals, nor in humans.

Because previous reports suggested that low doses of THC have sedating effects, the aim of the present study was to characterize in rats, the acute effects on sleep induced by the administration of low doses of THC by means of vaporization of a specific type of Cannabis (THC 11.5% and negligible amounts of other cannabinoids).

For this purpose, polysomnographic recordings in chronically prepared rats were performed during 6 h in the light and dark phases. Animals were treated with 0 (control), 40, 80 and 200 mg of Cannabis immediately before the beginning of recordings; the THC plasma concentrations with these doses were low (up to 6.7 ng/mL with 200 mg). A quantitative EEG analyses by means of the spectral power and coherence estimations was also performed for the highest Cannabis dose.

Compared to control, 200 mg of Cannabis increased NREM sleep time during the light phase, but only during the first hour of recording. Interestingly, no changes on sleep were observed during the dark (active) phase or with lower doses of Cannabis. Cannabis 200 mg also produced EEG power reductions in different cortices, mainly for high frequency bands during W and REM sleep, but only during the light phase. On the contrary, a reduction in the sleep spindles intra-hemispheric coherence was observed during NREM sleep, but only during the dark phase.

In conclusion, administration of low doses of THC by vaporization of a specific type of Cannabis produced a small increment of NREM sleep, but only during the light (resting) phase. This was accompanied by subtle modifications of high frequency bands power (during the light phase) and spindle coherence (during the dark phase), which are associated with cognitive processing.

Our results reassure the importance of exploring the sleep-promoting properties of Cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/30822492

https://www.sciencedirect.com/science/article/pii/S0091305718304714?via%3Dihub

Plant-Based Modulators of Endocannabinoid Signaling.

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Journal of Natural Products

“Extracts from Cannabis species have aided the discovery of the endocannabinoid signaling system (ECSS) and phytocannabinoids that possess broad therapeutic potential. Whereas the reinforcing effects of C. sativa are largely attributed to CB1 receptor agonism by Δ9-tetrahydrocannabinol (Δ9-THC), the observed medicinal effects of Cannabis arise from the combined actions of various compounds. In addition to compounds bearing a classical cannabinoid structure, naturally occurring fatty acid amides and esters resembling anandamide and 2-arachidonoyl glycerol isolated from non- Cannabis species are also valuable tools for studying ECSS function. This review highlights the potential of plant-based secondary metabolites from Cannabis and unrelated species as ECSS modulators.”

https://www.ncbi.nlm.nih.gov/pubmed/30816712

https://pubs.acs.org/doi/10.1021/acs.jnatprod.8b00874