Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol.

Abstract

“OBJECTIVES:

The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC.

METHODS:

Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected.

RESULTS:

Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects.

CONCLUSIONS:

These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/20838217

Efficacy of Crude Marijuana and Synthetic Delta-9-Tetrahydrocannabinol as Treatment for Chemotherapy-Induced Nausea and Vomiting: A Systematic Literature Review.

Abstract

“Purpose/Objectives: To synthesize the research to determine whether oral delta-9-tetrahydrocannabinol (THC) and smoked marijuana are effective treatments for chemotherapy-induced nausea and vomiting (CINV) and to evaluate side effects and patient preference of these treatments.Data Sources: Original research, review articles, and other published articles in CINAHL(R), MEDLINE(R), and Cochrane Library databases.Data Synthesis: Cannabinoids are effective in controlling CINV, and oral THC and smoked marijuana have similar efficacy. However, smoked marijuana may not be accessible or safe for all patients with cancer. Also, these drugs have a unique side-effect profile that may include alterations in motor control, dizziness, dysphoria, and decreased concentration.Conclusions: This synthesis shows that cannabinoids are more effective than placebo and comparable to antiemetics such as prochlorperazine and ondansetron for CINV.Implications for Nursing: Nurses should feel supported by the literature to recommend oral synthetic THC as a treatment for CINV to their patients and physician colleagues. Nurses should be cognizant of the side-effect profile for this medication and provide appropriate patient education.”

http://www.ncbi.nlm.nih.gov/pubmed/19596652

On the application of cannabis in paediatrics and epileptology.

Abstract

“An initial report on the therapeutic application of delta 9-THC (THC) (Dronabinol, Marinol) in 8 children resp. adolescents suffering from the following conditions, is given: neurodegenerative disease, mitochondriopathy, posthypoxic state, epilepsy, posttraumatic reaction. THC effected reduced spasticity, improved dystonia, increased initiative (with low dose), increased interest in the surroundings, and anticonvulsive action. The doses ranged from 0.04 to 0.12 mg/kg body weight a day. The medication was given as an oily solution orally in 7 patients, via percutaneous gastroenterostomy tube in one patient. At higher doses disinhibition and increased restlessness were observed. In several cases treatment was discontinued and in none of them discontinuing resulted in any problems. The possibility that THC-induced effects on ion channels and transmitters may explain its therapeutic activity seen in epileptic patients is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/15159680

Marijuana Compound Treats Schizophrenia with Few Side Effects:Clinical Trial

“A compound found in marijuana can treat schizophrenia as effectively as antipsychotic medications, with far fewer side effects, according to a preliminary clinical trial.

“Because it comes from marijuana, there are obvious political issues surrounding its use. Extracting it from the plant is also expensive. But the biggest barrier may be that CBD is a natural compound, and therefore can’t be patented the way new drugs are. That means that despite the possibility that it could outsell their current blockbuster antipsychotic drugs, pharmaceutical companies aren’t likely to develop it — a particularly striking fact when you consider that every major manufacturer of new generation antipsychotics in the U.S. has so far paid out hundreds of millions or billions of dollars in fines for mismarketing these drugs. Yet they still reaped huge profits.”

“For people with schizophrenia and their families, of course, it is likely to be infuriating that non-scientific issues like marijuana policy and patenting problems could stand in the way of a treatment that could potentially be so restorative. While it’s possible that these study results may not hold up or that researchers could discover problems related to long-term use of CBD,  it’s hard to imagine that they could be any worse than what patients already experience.”

Read more: http://healthland.time.com/2012/05/30/marijuana-compound-treats-schizophrenia-with-few-side-effects-clinical-trial/

History of cannabis as a medicine: a review

 

” Cannabis as a medicine was used before the Christian era in Asia, mainly in India. The introduction of cannabis in the Western medicine occurred in the midst of the 19th century, reaching the climax in the last decade of that century, with the availability and usage of cannabis extracts or tinctures. In the first decades of the 20th century, the Western medical use of cannabis significantly decreased largely due to difficulties to obtain consistent results from batches of plant material of different potencies. The identification of the chemical structure of cannabis components and the possibility of obtaining its pure constituents were related to a significant increase in scientific interest in such plant, since 1965. This interest was renewed in the 1990’s with the description of cannabinoid receptors and the identification of an endogenous cannabinoid system in the brain. A new and more consistent cycle of the use of cannabis derivatives as medication begins, since treatment effectiveness and safety started to be scientifically proven.”

 

“Cannabis Sativa (cannabis) is among the earliest plants cultivated by man. The first evidence of the use of cannabis was found in China, where archeological and historical findings indicate that that plant was cultivated for fibers since 4.000 B.C.1 With the fibers obtained from the cannabis stems, the Chinese manufactured strings, ropes, textiles, and even paper. Textiles and paper made from cannabis were found in the tomb of Emperor Wu (104-87 B.C.), of the Han dynasty.

 

“The Chinese also used cannabis fruits as food. These fruits are small (3 to 5 mm), elliptic, smooth, with a hard shell, and contain one single seed. The first evidence of the use of these seeds was found during the Han dynasty (206 B.C. – 220 A.D.). In the beginning of the Christian Era, with the introduction of new cultures, cannabis was no longer an important food in China, although, until today, the seeds are still used for making kitchen oil in Nepal.

 

“The use of cannabis as a medicine by ancient Chinese was reported in the world’s oldest pharmacopoeia, the pen-ts’ao ching which was compiled in the first century of this Era, but based on oral traditions passed down from the time of Emperor Shen-Nung, who lived during the years 2.700 B.C. Indications for the use of cannabis included: rheumatic pain, intestinal constipation, disorders of the female reproductive system, malaria, and others.In the beginning of the Christian Era, Hua T’o, the founder of Chinese surgery (A.D. 110 – 207), used a compound of the plant, taken with wine, to anesthetize patients during surgical operations.

 

“The Chinese used mainly the seeds of cannabis for medical purposes; therefore, it may be assumed that they were referring to that part of the plant when describing its medicinal properties. Until today, cannabis seeds continue to be used as a laxative by Chinese physicians. It is acknowledged that the seeds are practically deficient in D9-tetrahydrocannabinol (D9-THC), which is considered the plant’s main active constituent, and is mainly composed of essential fatty acids and proteins. Today some of these fatty acids are considered as having therapeutic effects, such as the g-linoleic acid, whose topical use is recommended for eczema and psoriasis, and its oral use for atherosclerosis, osteoporosis, rheumatoid arthritis, and other inflammatory diseases. In China, the medical use of cannabis never reached the importance it did in India.”

Read More: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000200015&lng=en&nrm=iso&tlng=en

Neutral antagonism at the cannabinoid 1 receptor: a safer treatment for obesity.

Abstract

“Obesity is a global problem with often strong neurobiological underpinnings. The cannabinoid 1 receptor (CB1R) was put forward as a promising drug target for antiobesity medication. However, the first marketed CB1R antagonist/inverse agonist rimonabant was discontinued, as its use was occasionally associated with negative affect and suicidality. In artificial cell systems, CB1Rs can become constitutively active in the absence of ligands. Here, we show that such constitutive CB1R activity also regulates GABAergic and glutamatergic neurotransmission in the ventral tegmental area and basolateral amygdala, regions which regulate motivation and emotions. We show that CB1R inverse agonists like rimonabant suppress the constitutive CB1R activity in such regions, and cause anxiety and reduced motivation for reward. The neutral CB1R antagonist NESS0327 does not suppress constitutive activity and lacks these negative effects. Importantly, however, both rimonabant and NESS0327 equally reduce weight gain and food intake. Together, these findings suggest that neutral CB1R antagonists can treat obesity efficiently and more safely than inverse agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/23070073