Tag Archives: THC

Tourette’s syndrome.

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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

Medicinal use of cannabis: history and current status.

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Abstract

“OBJECTIVE:

To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids.

METHODS:

The literature on therapeutic uses of cannabis and cannabinoids was assessed with respect to type of study design, quality and variability of data, independent replications by the same or other investigators, magnitude of effects, comparison with other available treatments and reported adverse effects. The results of this review were also compared with those of major international reviews of this topic in the past five years.

CONCLUSIONS:

Pure tetrahydrocannabinol and several analogues have shown significant therapeutic benefits in the relief of nausea and vomiting, and stimulation of appetite in patients with wasting syndrome. Recent evidence clearly demonstrates analgesic and anti-spasticity effects that will probably prove to be clinically useful. Reduction of intraocular pressure in glaucoma and bronchodilation in asthma are not sufficiently strong, long lasting or reliable to provide a valid basis for therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently promising to warrant further properly designed clinical trials. There is still a major lack of long term pharmacokinetic data and information on drug interactions. For all the present and probable future uses, pure cannabinoids, administered orally, rectally or parenterally, have been shown to be effective, and they are free of the risks of chronic inflammatory disease of the airways and upper respiratory cancer that are associated with the smoking of crude cannabis. Smoking might be justified on compassionate grounds in terminally ill patients who are already accustomed to using cannabis in this manner. Future research will probably yield new synthetic analogues with better separation of therapeutic effects from undesired psychoactivity and other side effects, and with solubility properties that may permit topical administration in the eye, or aerosol inhalation for rapid systemic effect without the risks associated with smoke inhalation.”

http://www.ncbi.nlm.nih.gov/pubmed/11854770

Recent developments in the therapeutic potential of cannabinoids.

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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.

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“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

The Therapeutic Potential of Cannabis and Cannabinoids

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“Background

Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany.”

“Therapeutic potential

Cannabis preparations exert numerous therapeutic effects. They have antispastic, analgesic, antiemetic, neuroprotective, and anti-inflammatory actions, and are effective against certain psychiatric diseases. Currently, however, only one cannabis extract is approved for use. It contains THC and CBD in a 1:1 ratio and was licensed in 2011 for treatment of moderate to severe refractory spasticity in multiple sclerosis (MS). In June 2012 the German Joint Federal Committee (JFC, Gemeinsamer Bundesausschuss) pronounced that the cannabis extract showed a “slight additional benefit” for this indication and granted a temporary license valid up to 2015.”

“The cannabis extract, which goes by the generic name nabiximols, has been approved by regulatory bodies in Germany and elsewhere for use as a sublingual spray. In the USA, dronabinol has been licensed since 1985 for the treatment of nausea and vomiting caused by cytostatic therapy and since 1992 for loss of appetite in HIV/Aids-related cachexia. In Great Britain, nabilone has been sanctioned for treatment of the side effects of chemotherapy in cancer patients.”

Results

“Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting.”

Conclusion

“There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442177/

 

[Cannabis and cannabinoids as drugs].

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Abstract

“BACKGROUND:

Cannabis has been used throughout human history. Delta (9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. THC metabolises to 11-OH-THC and further to THC-acid, which is an inactive metabolite. We present an overview of the pharmacokinetics and pharmacodynamics of cannabinoids.

MATERIAL AND METHOD:

This article is based on selected literature with an emphasis on the pharmacodynamics of cannabinoids.

RESULTS AND INTERPRETATION:

It has been demonstrated that mammalian tissues express cannabinoid receptors (CB1, CB2 and most probably CB3) and endogenous ligands for these. Knowledge of these receptors has lead to the development of components that stimulate (CB-agonists) or block their function (CB-antagonists). This opens up for the study of any potential therapeutic effects of cannabinoids. Research on a possible therapeutic potential of cannabinoids should however not overshadow the well-documented negative effects of cannabis; i.e. impaired cognitive functions, intoxication and an increased risk for development of psychosis and psychotic symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/17332810

Pharmacokinetics and pharmacodynamics of cannabinoids.

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Abstract

“Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30-90 minutes, reach their maximum after 2-3 hours and last for about 4-12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.”

http://www.ncbi.nlm.nih.gov/pubmed/12648025

Cannabinoids in clinical practice.

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Abstract

“Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette’s syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.”

http://www.ncbi.nlm.nih.gov/pubmed/11152013

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

CB receptor ligands from plants.

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Abstract

“Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.”

http://www.ncbi.nlm.nih.gov/pubmed/18289087