Tag Archives: delta(9)-tetrahydrocannabinol (delta(9)-THC)

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

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Abstract

  “Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.”

http://www.ncbi.nlm.nih.gov/pubmed/14738597

The endogenous cannabinoid system and the treatment of marijuana dependence.

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Abstract

“The active principle of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), exerts its pharmacological effects by binding to selective receptors present on the membranes of neurons and other cells. These cannabinoid receptors are normally engaged by a family of lipid mediators, called endocannabinoids, which are thought to participate in the regulation of a diversity of brain functions, including pain, mood, appetite and memory. Marijuana use may lead to adaptive changes in endocannabinoid signaling, and these changes might contribute to effects of marijuana as well as to the establishment of marijuana dependence. In the present article, I outline current views on how endocannabinoid substances are produced, released, and deactivated in the brain. In addition, I review recent progress on the development of pharmacological agents that interfere with endocannabinoid deactivation and discuss their potential utility in the treatment of marijuana dependence and other aspects of drug abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/15464150

Marijuana Successfully Treats Tourette’s Syndrome, Study Shows

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“Thursday, 11 March 1999

German researchers report that the consumption of the marijuana compound THC alleviates symptoms of Tourette’s Syndrome. The researchers published their findings in this month’s issue of the American Journal of Psychiatry.

“Earlier reports suggested beneficial effects in Tourette’s syndrome when smoking marijuana,” the German research team wrote. “We report a successful treatment of Tourette’s syndrome with delta-9-tetrahydocannabinol, the major psychoactive ingredient of marijuana.”

Tourette’s syndrome is a complex neuropsychiatric disorder that is characterized by sudden spasms, so called “tics,” that occur especially in the face, neck, and shoulders.

The researchers found that a 25-year-old patient treated with 10 mg of THC experienced marked improvement of both vocal and motor tics associated with behavioral disorders. “The improvement began 30 minutes after treatment and lasted for about seven hours,” the researchers reported. “No adverse effects occurred.”

Researchers stated, “This is the first report of a successful treatment of Tourette’s syndrome with delta-9-THC.” They said they are planning to confirm their preliminary results in an upcoming double-blind, placebo controlled, crossover study.

NORML board member Dr. Lester Grinspoon of Harvard Medical School called inhaled marijuana’s effects on patients suffering from Tourette’s “impressive,” and said that the drug holds tremendous potential as a course of treatment for the disease.

For more information, please contact either Allen St. Pierre of The NORML Foundation @ (202) 483-8751 or NORML board member Dr. Lester Grinspoon of Harvard Medical School @ (617) 277-3621.”

http://norml.org/news/1999/03/11/marijuana-successfully-treats-tourette-s-syndrome-study-shows

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

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“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.

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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

Therapeutic potential of cannabinoids in CNS disease.

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Abstract

“The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson’s disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/12617697