Tag Archives: Delta-9-Tetrahydrocannabinol

A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

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“One of the most devastating forms of cancer is glioblastoma multiforme (grade IV astrocytoma), the most frequent class of malignant primary brain tumours. Current standard therapeutic strategies for the treatment of glioblastoma multiforme (surgical resection and focal radiotherapy) are only palliative…”

“The hemp plant Cannabis sativa L. produces approximately 60 unique compounds known as cannabinoids, of which Δ9-tetrahydrocannabinol (THC) is the most important owing to its high potency and abundance in cannabis. Δ9-Tetrahydrocannabinol exerts a wide variety of biological effects by mimicking endogenous substances – the so-called endocannabinoids – that bind to and activate specific cell surface receptors. cannabinoids have been proposed as potential antitumoral agents owing to their ability to inhibit the growth and angiogenesis of various types of tumour xenografts in animal models.”

“Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration… Cannabinoid delivery was safe and could be achieved without overt psychoactive effects…. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/

Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L

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“The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Δ9-THC and other cannabinoids… Results of this study show that Δ9-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.”

“Cannabis sativa L. is one of the most widely used plants for both recreational and medicinal purposes. To date a total of 525 natural constituents covering several chemical classes have been isolated and identified from C. sativa. The cannabinoids belong to the chemical class of terpenophenolics, of which 85 have been uniquely identified in cannabis, including the most psychoactive cannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). The most common natural plant cannabinoids (phytocannabinoids) are: Δ9-THC, cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN). Several of the identified cannabinoids are both chemically and pharmacologically poorly characterized due to insufficient isolated amounts; however, the pharmacology of Δ9-THC has been widely studied, and it is regarded as the main psychoactive constituent of cannabis.”

“The psychological and physiological effects of cannabis have been extensively characterized, including euphoria, analgesia, sedation, memory and cognitive impairment, appetite stimulation, and anti-emesis. Most of these effects have been primarily attributed to Δ9-THC. Major advances in the field of cannabinoid research were achieved following the unraveling of the molecular mechanism underlying the actions of Δ9-THC and the discovery of the endocannabinoid system. The endocannabinoid system is regarded as a neuromodulator, and is comprised of cannabinoid receptors (primarily CB1 and CB2 receptors), their endogenous ligands, and enzymes responsible for the synthesis and metabolism of these ligands.”

“In addition to the established effects of cannabis, it is well recognized that mood elevation is one of the components of the complex experience elicited by cannabis. Much of our knowledge regarding cannabis effect on mood and anxiety is based on individual reports following cannabis use for medicinal or recreational purposes. Several anecdotal reports describe the antidepressant effect of cannabis, with patients confirming beneficial outcomes from its use in primary or secondary depressive disorders…”

“In conclusion, our results show that phytocannabinoids, including Δ9-THC, CBD, and CBC, exert antidepressant-like actions in animal models of behavioral despair. The exact mechanism underlying such activity is still unclear and confounded by the fact that these compounds have varying binding profiles to the established cannabinoid CB1 as well as to non CB1 receptors. The results support the effect of phytocannabinoids on mood disorders and provide potential leads for further studies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

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  “Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Treatment of Tourette syndrome with cannabinoids.

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Abstract

“Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC) and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS) several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a large number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.”

http://www.ncbi.nlm.nih.gov/pubmed/23187140

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

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“Autism is a behaviorally defined neurodevelopmental disorder characterized by impairments in social interaction and communication and repetitive/stereotyped behaviors . The cause of autism is not completely understood and there is no effective cure. However, genetic and environmental factors and the interaction between genes and environment are known to play a role in Autism Spectrum Disorders (ASDs)…

Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

It is tempting to suggest the evaluation of Δ9-THC or other cannabinoids with reduced psychoactivity in irritability, tantrums and self-injurious behavior associated with autistic individuals.

 The rationale for this novel hypothesis arises from the discovery that the endocannabinoid system is one of the most abundant physiological control systems in animals and humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137184/

Would some cannabinoids ameliorate symptoms of autism?

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“Cannabidiol (CBD) is a major nonpsychotropic constituent of cannabis sativa, which unlike the other major constituent delta9-tetrahydrocannabinol (delta9-THC), is virtually inactive at both of its central nervous system receptors. In one study, cell-based calcium mobilization and electrophysiological assays were used to identify and characterize several novel cannabinoid TRPV2 agonists in cultured rat dorsal root ganglion neurons. Among these, CBD was found to be the most robust and potent, followed by delta9-THC and cannabinol. Those cannabinoids may, accordingly, possess the ability, due to their action as TRPV2 agonists, to increase the release of both oxytocin and vasopressin enhancing the stimulation of oxytocin receptor and V1a receptors at the same time. CBD displays a plethora of other actions including anticonvulsive, sedative, hypnotic, antipsychotic, anti-inflammatory and neuroprotective properties. CBD and delta9-THC are components of drugs commercialized, in certain countries, as treatments for neuropathic pain, overactive bladder, and spasticity in patients suffering from multiple sclerosis. Thus, despite their action on oxytocin and vasopressin release, CBD and delta9-THC may help in improving symptoms of ASD by their sedative, antipsychotic, anticonvulsant and tranquilizing effects. In addition, the cannabinoid system has already been shown to be implicated in social behavior in rats.
 
The administration of cannabinoids for children and adolescents suffering from ASD is a controversial legal and ethical issue. Instead, those cannabinoids may be tested when administered to animals presenting autistic symptoms. Animal models of autistic symptoms exist especially in rodents that have their oxytocin and/or vasopressin function impaired such as mice or rats lacking the oxytocin or vasopressin gene or one of their receptors]. Whenever cannabinoids were found efficient in animal models of autism, the rationale supporting their efficacy may outweigh their legal and ethical adversities, when administered to children in the setting of randomized controlled studies.”
 

[Cannabinoids in the control of pain].

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Abstract

“Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy. Only recently the medical community highlighted the pharmacological scientific bases of its effects. The most important active principle, Delta-9-tetrahydrocannabinol, was identified in the second half of the last century, and subsequently two receptors were identified and cloned: CB1 that is primarily present in the central nervous system, and CB2 that is present on the cells of the immune system. Endogenous ligands, called endocannabinoids, were characterized. The anandamide was the first one to be discovered. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids are analgesic, and their activity is comparable to the weak opioids. Furthermore, parallels exist between opioid and cannabinoid receptors, and evidence is accumulating that the two systems sometimes may operate synergistically. The interest of the pharmaceutical companies led to the production of various drugs, whether synthetic or natural derived. The good ratio between the polyunsatured fatty acids omega-3 and omega-6 of the oil of Cannabis seeds led to reduction of the phlogosis and an improvement of the pain symptoms in patients with chronic musculo-skeletal inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/19388223

Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside.

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“Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need…

In humans, effects of smoked marijuana, synthetic Delta(9)-THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both Delta(9)-THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment…

Evidence for the use of Cannabis sativa as a treatment for pain can be traced back to the beginnings of recorded history…

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755639/

The Endocannabinoid System and Pain

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“Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Endocannabinoids … Continue reading →

Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.

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Abstract

“OBJECTIVE:

To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.

DATA SOURCES:

Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.

STUDY SELECTION AND DATA EXTRACTION:

Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.

DATA SYNTHESIS:

The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.

CONCLUSIONS:

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.”

http://www.ncbi.nlm.nih.gov/pubmed/16449552