Category Archives: THC (Delta-9-Tetrahydrocannabinol)

The endocannabinoid nervous system: unique opportunities for therapeutic intervention.

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“The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid-based therapeutics has focused predominantly on the CB1 receptor, based on its predominant and abundant localization in the CNS.

Like most of the known cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for both receptor subtypes.

Clinical studies show that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid transmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportunities for therapeutic intervention.

This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved safety and efficacy profiles.”

http://www.ncbi.nlm.nih.gov/pubmed/11448725

Worth Repeating: Marijuana Treats Anxiety and Depression

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HanusAndMechoulam.jpg
Lumír Ondřej Hanuš (left), discoverer of endogenous ligand, anandamide, from brain (1992) and Raphael Mechoulam (right), discoverer of psychoactive compound, (-)-trans-delta-9-tetrahydrocannabinol, from Cannabis sativa L. (1964). Both compounds bind to the CB1 and 2 cannabinoid receptors in the brain.
“This post is dedicated to these two great medical researchers. The fathers of homeostatic cannabinoid based medicine:
 
Lumír Ondřej Hanuš, discoverer of the endogenous ligand, anandamide, from the brain (1992) and Raphael Mechoulam, discoverer of the psychoactive compound, THC, from Cannabis sativa (1964). Both compounds bind to the CB1 and 2 cannabinoid receptors in the brain.
 
These two men need to be nominated and awarded the 2012  Nobel Prize in medicine for discovering the healing potential of cannabis. Their discoveries will save the human race a great deal of suffering. Thank you for your gift to humanity, gentlemen.”
 

Discovery and development of endocannabinoid-hydrolyzing enzyme inhibitors.

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“Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that are produced on demand in response to elevated intracellular calcium levels. They recognize and activate the cannabinoid CB(1) and CB(2) receptors, the molecular targets for Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in marijuana evoking several beneficial therapeutic effects. However, in vivo the cannabimimetic effects of AEA and 2-AG remain weak owing to their rapid inactivation by FAAH and MGL, respectively. The inactivation of FAAH and MGL by specific enzyme inhibitors increases the levels of AEA and 2-AG, respectively, producing therapeutic effects such as pain relief and depression of anxiety.”

http://www.ncbi.nlm.nih.gov/pubmed/20370710

Role of endocannabinoid system in mental diseases.

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“In the last decade, a large number of studies using Delta9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation.

 Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports of the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions or psychiatric illness…

 Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabinoid system to novel opportunities for therapeutic intervention and its effects on the central nervous system.”

http://www.ncbi.nlm.nih.gov/pubmed/15325960

Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives.

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“Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals. The heterogeneity of cannabis-induced psychological outcomes reflects a complex network of molecular interactions between the key neurobiological substrates of anxiety and fear and the endogenous cannabinoid system, mainly consisting of the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol (2-AG) and two receptors, respectively termed CB1 and CB2. The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself.

The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the side effects associated with cannabis consumption. In addition the article presents some promising patents on cannabinoid-related agents.”

http://www.ncbi.nlm.nih.gov/pubmed/22280339

Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

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“The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats…

…both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects…

The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals…”

http://www.ncbi.nlm.nih.gov/pubmed/19406854

Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol.

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Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC)…

The administration of a low dose of THC produced clear anxiolytic-like responses…

CONCLUSIONS:

These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.”

http://www.ncbi.nlm.nih.gov/pubmed/12185408

Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring.

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“A prospective observational study assessed the effectiveness of adjuvant nabilone (Cesamet) therapy in managing pain and symptoms experienced by advanced cancer patients… When compared with those not taking nabilone, patients using this cannabinoid had a lower rate of starting nonsteroidal anti-inflammatory agents, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron and a greater tendency to discontinue these drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/18402303

The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety.

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“The anxiolytic properties of nabilone, a synthetic cannabinoid resembling the natural cannabinoids, were studied in 25 outpatients suffering from anxiety. The drug was compared with a placebo in a double-blind manner over a 28-day treatment period. Patients were seen weekly by the physician and were rated by the Hamilton Rating Scale for Anxiety and the Patient’s Global Evaluation as well as by patient-rated evaluations. The results of the study showed a dramatic improvement in anxiety in the nabilone group when compared with placebo (P less than 0.001). Side effects reported were dry mouth, dry eyes, and drowsiness. Patients did not report any of the subjective “altered state” experience of marihuana.”

http://www.ncbi.nlm.nih.gov/pubmed/6117575

Experience with the synthetic cannabinoid nabilone in chronic noncancer pain.

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“Chronic noncancer pain includes a heterogeneous group of disorders and is often refractory to treatment. Cannabis products have historically been used for chronic pain and are attracting renewed pharmaceutical interest. Nabilone is a synthetic cannabinoid licensed in Canada for the treatment of severe nausea and vomiting associated with cancer chemotherapy. We have used nabilone off-label for the treatment of chronic noncancer pain since 1999. In this article, we review our clinical experience of 20 adult patients with chronic noncancer pain who had been treated with nabilone and followed up for an average of 1.5 years. Prior to nabilone therapy, patients had used a wide range of therapies, including 11 who had used cannabis. Fifteen patients reported subjective overall improvement with nabilone, and nine reported reduced pain intensity. Beneficial effects on sleep and nausea were the main reasons for continuing use. Intolerable side effects were experienced in three patients (palpitations, urinary retention, dry mouth). Nabilone may be a useful addition to pain management and should be further evaluated in randomized controlled trials.”

http://www.ncbi.nlm.nih.gov/pubmed/16533193