Tag Archives: marijuana

Treatment of Tourette Syndrome with Delta-9-Tetrahydrocannabinol (9-THC): No Influence on Neuropsychological Performance

Posted on by

“Previous studies provide evidence that marijuana (Cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, respectively, are effective in the treatment of tics and behavioral problems in Tourette syndrome (TS). It, therefore, has been speculated that the central cannabinoid receptor system might be involved in TS pathology. However, in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and/or long-term cognitive deficits. In this randomized double-blind placebo-controlled study, we investigated the effect of a treatment with up to 10 mg Delta(9)-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS. During medication and immediately as well as 5-6 weeks after withdrawal of Delta(9)-THC treatment, no detrimental effect was seen on learning curve, interference, recall and recognition of word lists, immediate visual memory span, and divided attention. Measuring immediate verbal memory span, we even found a trend towards a significant improvement during and after treatment. Results from this study corroborate previous data suggesting that in patients suffering from TS, treatment with Delta(9)-THC causes neither acute nor long-term cognitive deficits. Larger and longer-duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS.”

“Anecdotal reports and two controlled studies provide evidence that marijuana (Cannabis sativa) and delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of marijuana, respectively, are effective in the treatment of tics and behavioral problems in TS.”

“In conclusion, our data are in agreement with anecdotal reports and a pilot study suggesting that -THC treatment in patients suffering from TS has no detrimental effect on neuropsychological performance. We hypothesize that the effects of -THC on cognition in TS patients might be different from those in healthy marijuana users because of the pathology of the disease. Since there is evidence that tics can be improved by THC, an involvement of the central CB1 receptor system in TS pathology has been suggested. However, larger and longer-duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS.”

http://www.nature.com/npp/journal/v28/n2/full/1300047a.html

Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance.

Posted on by

Abstract

“Previous studies have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (delta9-THC), the major psychoactive ingredient of marijuana, are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users, we performed a randomized double-blind placebo-controlled crossover trial for delta9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of delta9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance. Using a variety of neuropsychological tests, we found no significant differences after treatment with delta9-THC compared to placebo treatment in verbal and visual memory, reaction time, intelligence, sustained attention, divided attention, vigilance, or mood. Only when using the Symptom Checklist 90-R (SCL-90-R) did our data provide evidence for a deterioration of obsessive-compulsive behavior (OCB) and a trend towards an increase in phobic anxiety. However, these results should be interpreted with caution as SCL-90-R has known limitations on measuring OCB. We suggest that the increase in phobic anxiety is mainly due to the fact that a single-dose treatment rules out the possibility of administering the dosage slowly. In contrast to results obtained from healthy marijuana users, a single-dose treatment with delta9-THC in patients suffering from TS does not cause cognitive impairment. We therefore suggest that further investigations should concentrate on the effects of a longer-term therapy of TS with delta9-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/11229617

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

Posted on by

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

Tourette’s syndrome.

Posted on by

Abstract

“Tourette’s syndrome (TS) is a chronic disorder characterized by motor and vocal tics and a variety of associated behaviour disorders. Because current therapy is often unsatisfactory, there is expanding interest in new therapeutic strategies that are more effective, cause less side effects and ameliorate not only tics but also behavioural problems. From anecdotal reports and preliminary controlled studies it is suggested that – at least in a subgroup of patients – cannabinoids are effective in the treatment of TS. While most patients report beneficial effects when smoking marijuana (Cannabis sativa L.), available clinical trials have been performed using oral Δ⁹-tetrahydrocannabinol (THC). In otherwise treatment-resistant TS patients, therefore, therapy with THC should not be left unattempted. To date, it is unknown whether other drugs that interact with the endocannabinoid receptor system might be more effective in the treatment of TS than smoked marijuana or pure THC. Since it has been suggested that abnormalities within the endocannabinoid receptor system might underlie TS pathophysiology, it would be of interest to investigate the effect of substances that for example bind more selectively to the central cannabinoid receptor or inhibit the uptake or the degradation of different endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/21104394

Recent developments in the therapeutic potential of cannabinoids.

Posted on by

Abstract

“OBJECTIVE:

To examine the recent evidence that marijuana and other cannabinoids have therapeutic potential.

METHODS:

Literature published since 1997 was searched using the following terms: cannabinoid, marijuana, THC, analgesia, cachexia, glaucoma, movement, multiple sclerosis, neurological, pain, Parkinson, trial, vomiting. Qualifying clinical studies were randomized, double-blind, and placebo-controlled. Selected open-label studies and surveys are also discussed.

RESULTS:

A total of 15 independent, qualifying clinical trials were identified, of which only three had more than 100 patients each. Two large trials found that cannabinoids were significantly better than placebo in managing spasticity in multiple sclerosis. Patients self-reported greater sense of motor improvement in multiple sclerosis than could be confirmed objectively. In smaller qualifying trials, cannabinoids produced significant objective improvement of tics in Tourette’s disease, and neuropathic pain. A new, non-psychotropic cannabinoid also has analgesic activity in neuropathic pain. No significant improvement was found in levodopa-induced dyskinesia in Parkinson’s Disease or post-operative pain. No difference from active placebo was found for management of cachexia in a large trial. Some immune system parameters changed in HIV-1 and multiple sclerosis patients treated with cannabinoids, but the clinical significance is unknown. Quality of life assessments were made in only three of 15 qualifying clinical trials.

CONCLUSION:

Cannabinoids may be useful for conditions that currently lack effective treatment, such as spasticity, tics and neuropathic pain. New delivery systems for cannabinoids and cannabis-based medicinal extracts, as well as new cannabinoid derivatives expand the options for cannabinoid therapy. More well-controlled, large clinical tests are needed, especially with active placebo.”

http://www.ncbi.nlm.nih.gov/pubmed/15895873

Cannabinoids in medicine: A review of their therapeutic potential.

Posted on by

“In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish.

For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described.

 Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette’s syndrome, epilepsy and glaucoma.”

http://www.ncbi.nlm.nih.gov/pubmed/16540272

Cannabinoids in health and disease

Posted on by

Abstract

“Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable – instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and – in cases where it is impossible to separate the desired clinical action and the psychoactivity – just to monitor these side effects carefully.”

Cancer

“The antiproliferative action of cannabinoids on cancer cells was first noticed in the 1970s. Since then cannabinoids were found to act on various cancer cell lines, through various mechanisms. Cannabinoids were also found to be suppressors of angiogenesis and tumor invasion. Our knowledge on the anticancer activity of cannabinoids is rapidly expanding.”

Conclusion

“Many drugs used today can cause addiction and are misused and abused, for example opiates, cocaine, benzodiazepines, barbiturates, cholinergic agonists, ketamine, dopaminergic agonists, amphetamines, and others. Nevertheless they are still an important part of our pharmacopeia. Marijuana was used for centuries as a medicinal plant, but during the last century, because of its abuse and addictive potential it was taken out of clinical practice. Now, we believe that its constituents and related compounds should be brought back to clinical use. The reasons are: (i) the therapeutic potential of CB1 agonists is huge, as described in this review; (ii) for local action, topical CB1 agonists, or agonists that do not penetrate the blood-brain barrier, can be used; (iii) cannabinoids acting specifically on CB2 receptors, which cause no psychoactivity, may be used on peripheral targets (such as osteoporosis, which is only one of many examples); (iv) there are additional, new cannabinoid targets distinct from the CB1/CB2 receptors which do not cause psychoactivity; (v) there are cannabinoids, such as CBD, which do not cause psychoactivity, but have various therapeutic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202504/

Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications.

Posted on by

“Much progress has been achieved in cannabinoid research. A major breakthrough in marijuana-cannabinoid research has been the discovery of a previously unknown but elaborate endogenous endocannabinoid system (ECS), complete with endocannabinoids and enzymes for their biosynthesis and degradation with genes encoding two distinct cannabinoid (CB1 and CB2) receptors (CBRs) that are activated by endocannabinoids, cannabinoids, and marijuana use.

Physical and genetic localization of the CBR genes CNR1 and CNR2 have been mapped to chromosome 6 and 1, respectively. A number of variations in CBR genes have been associated with human disorders including osteoporosis, attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), drug dependency, obesity, and depression. Other family of lipid receptors including vanilloid (VR1) and lysophosphatidic acid (LPA) receptors appear to be related to the CBRs at the phylogenetic level. The ubiquitous abundance and differential distribution of the ECS in the human body and brain along with the coupling to many signal transduction pathways may explain the effects in most biological system and the myriad behavioral effects associated with smoking marijuana. The neuropharmacological and neuroprotective features of phytocannabinoids and endocannabinoid associated neurogenesis have revealed roles for the use of cannabinoids in neurodegenerative pathologies with less neurotoxicity. The remarkable progress in understanding the biological actions of marijuana and cannabinoids have provided much richer results than previously appreciated cannabinoid genomics and raised a number of critical issues on the molecular mechanisms of cannabinoid induced behavioral and biochemical alterations. These advances will allow specific therapeutic targeting of the different components of the ECS in health and disease.

 This review focuses on these recent advances in cannabinoid genomics and the surprising new fundamental roles that the ECS plays in the retrograde signaling associated with cannabinoid inhibition of neurotransmitter release to the genetic basis of the effects of marijuana use and pharmacotherpeutic applications and limitations. Much evidence is provided for the complex CNR1 and CNR2 gene structures and their associated regulatory elements. Thus, understanding the ECS in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19897083

Endocannabinoids and cannabinoid receptor genetics.

Posted on by

“This review presents the remarkable advances that have been achieved in marijuana (cannabinoid) research, with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the human body and brain.

 The last decade has seen more rapid progress in marijuana research than any time in the thousands of years that marijuana has been used by humans, particularly in cannabinoid genomics. The cDNA and genomic sequences encoding G protein-coupled cannabinoid receptors (Cnrs) from several species have now been cloned. Endogenous cannabinoids (endocannabinoids), synthetic and hydrolyzing enzymes and transporters that define neurochemically-specific cannabinoid brain pathways have been identified. Endocannabinoid lipid signaling molecules alter activity at G protein-coupled receptors (GPCR) and possibly at anandamide-gated ion channels, such as vanilloid receptors. Availability of increasingly-specific CB1 and CB2 Cnr antagonists and of CB1 and CB2 Cnr knockout mice have increased our understanding of these cannabinoid systems and provides tantalizing evidence for even more G protein-coupled Cnrs. Initial studies of the Cnr gene structure, regulation and polymorphisms whet our appetite for more information about these interesting genes, their variants and roles in vulnerabilities to addictions and other neuropsychiatric disorders. Behavioral studies of cannabinoids document the complex interactions between rewarding and aversive effects of these drugs.

Pursuing cannabinoid-related molecular, pharmacological and behavioral leads will add greatly to our understanding of endogenous brain neuromodulator systems, abused substances and potential therapeutics. This review of CB1 and CB2 Cnr genes in human and animal brain and their neurobiological effects provide a basis for many of these studies.

Therefore, understanding the physiological cannabinoid control system in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/12015198

Established and potential therapeutic applications of cannabinoids in oncology.

Posted on by

Abstract

“Cannabis occurs naturally in the dried flowering or fruiting tops of the Cannabis sativa plant. Cannabis is most often consumed by smoking marihuana. Cannabinoids are the active compounds extracted from cannabis. Recently, there has been renewed interest in cannabinoids for medicinal purposes. The two proven indications for the use of the synthetic cannabinoid (dronabinol) are chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Other possible effects that may prove beneficial in the oncology population include analgesia, antitumor effect, mood elevation, muscle relaxation, and relief of insomnia. Two types of cannabinoid receptors, CB1 and CB2, have been detected. CB1 receptors are expressed mainly in the central and peripheral nervous system. CB2 receptors are found in certain nonneuronal tissues, particularly in the immune cells. Recent discovery of both the cannabinoid receptors and endocannabinoids has opened a new era in research on the pharmaceutical applications of cannabinoids. The use of cannabinoids should be continued in the areas indicated, and further studies are needed to evaluate other potential uses in clinical oncology.”

http://www.ncbi.nlm.nih.gov/pubmed/12618922