Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists.

Abstract

“Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB(1)) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Delta(9)-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB(1) receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB(1) receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB(1) receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.”

http://www.ncbi.nlm.nih.gov/pubmed/20218784

Marijuana Compound Effective In Treating Tourette’s Syndrome, Study Says

“Thursday, 15 May 2003

Hanover, Germany: A primary compound in marijuana, delta-9-tetrahydrocannabinol (THC), is effective in reducing “tics” in patients suffering from Tourette’s Syndrome (TS), according to clinical trail data published in a recent edition of the Journal of Clinical Psychiatry. Tourette’s Syndrome is a complex neuropsychiatric disorder characterized by motor tics (sudden spasms especially in the facial muscles, neck and shoulders) and one or more vocal tics.

Twenty-four patients participated in the double-blind placebo-controlled trial over a period of six weeks. Treatment with up to 10 mg of THC resulted in significant improvement of tic severity, authors wrote. No serious adverse effects to the treatment were reported.

In a separate article published in Neuropsychopharmacology, authors elaborated, “No detrimental effect was seen on learning curve, interference, recall and recognition of word lists, immediate visual memory span, and divided attention” from THC during or after the treatment.

The 24-patient study confirmed previous smaller patient trials that also found THC to be effective in the treatment of tics and behavioral problems in patients with Tourette’s Syndrome.”

http://norml.org/news/2003/05/15/marijuana-compound-effective-in-treating-tourette-s-syndrome-study-says

Oral delta 9-tetrahydrocannabinol improved refractory Gilles de la Tourette syndrome in an adolescent by increasing intracortical inhibition: a case report.

Abstract

“OBJECTIVE:

To describe the clinical course of the Delta 9-tetrahydrocannabinol (Delta 9-THC) treatment of a boy with Gilles de la Tourette Syndrome (TS) and comorbid attention-deficit/hyperactivity disorder (ADHD) in relation to Delta 9-THC plasma levels and intracortical inhibition measured by transcranial magnetic stimulation.

METHODS:

The clinical course and pharmacological and neurophysiological measures are reported in a 15-year-old boy with treatment refractory TS plus ADHD leading to severe physical and psychosocial impairment.

RESULTS:

Administration of Delta 9-THC improved tics considerably without adverse effects, allowing parallel stimulant treatment of comorbid ADHD. Along with the Delta 9-THC treatment, intracortical inhibition was increased, reflected in the enhanced short-interval intracortical inhibition and the prolongation of the cortical silent period.

CONCLUSIONS:

Our observation suggests that Delta 9-THC might be a successful alternative in patients with severe TS refractory to classic treatment. Particularly in the case of stimulant-induced exacerbation of tics, Delta 9-THC might enable successful treatment of comorbid ADHD. The enhancement of intracortical inhibition might be mediated by modulating release of several neurotransmitters including dopamine and gamma-aminobutyric acid. Further studies are needed to substantiate our findings.”

http://www.ncbi.nlm.nih.gov/pubmed/20520294

Cannabinoids reduce symptoms of Tourette’s syndrome.

Abstract

“Currently, the treatment of Tourette’s syndrome (TS) is unsatisfactory. Therefore, there is expanding interest in new therapeutical strategies. Anecdotal reports suggested that the use of cannabis might improve not only tics, but also behavioural problems in patients with TS. A single-dose, cross-over study in 12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated that Delta9-tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, reduces tics in TS patients. No serious adverse effects occurred and no impairment on neuropsychological performance was observed. If well-established drugs either fail to improve tics or cause significant adverse effects, in adult patients, therapy with Delta9-THC should be tried. At present, it remains unclear whether herbal cannabis, different natural or synthetic cannabinoid CB1-receptor agonists or agents that interfere with the inactivation of endocannabinoids, may have the best adverse effect profile in TS.”

http://www.ncbi.nlm.nih.gov/pubmed/14521482

Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial.

“Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS).

This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS.

CONCLUSION:

Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology.”

https://www.ncbi.nlm.nih.gov/pubmed/12716250

“Our results provide more evidence that THC is effective and safe in the treatment of tics.” http://www.psychiatrist.com/jcp/article/Pages/2003/v64n04/v64n0417.aspx

Treatment of Tourette’s syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial.

Abstract

“Anecdotal reports in Tourette’s syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette’s syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette’s syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette’s syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore “complex motor tics” (p = 0.015) and a trend towards a significant improvement for the subscores “motor tics” (p = 0.065), “simple motor tics” (p = 0.093), and “vocal tics” (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results.”

http://www.ncbi.nlm.nih.gov/pubmed/11951146

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

“Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis (cell death) in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children…

 Our study shows that treatment with the cannabinoid receptor agonists HU210 (cloned THC from Hebrew University) and Delta(9)-tetrahydrocannabinol (THC from cannabis) lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis…

These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.”

Full text: http://mct.aacrjournals.org/content/8/7/1838.long

Anti-tumoral Action of Cannabinoids

“Delta9-Tetrahydrocannabinol, the main active component of marijuana… Here, we show that intratumoral administration of Delta9-tetrahydrocannabinol… induced a considerable regression of malignant gliomas… Cannabinoid treatment did not produce any substantial neurotoxic effect… cannabinoids signal apoptosis (cell death/suicide) by a pathway involving cannabinoid receptors… These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.”

‎”Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death…”

http://www.ncbi.nlm.nih.gov/pubmed/10700234

Single-dose Pharmacokinetics and Tolerability of Oral Delta-9-Tetrahydrocannabinol in Patients with Amyotrophic Lateral Sclerosis

“Single-dose Pharmacokinetics and Tolerability of Oral Delta-9-Tetrahydrocannabinol in Patients with Amyotrophic Lateral Sclerosis… Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS)…”

http://www.ncbi.nlm.nih.gov/pubmed/22594565