Tag Archives: medications

Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex

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   “Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6–10 marijuana cigarettes/day, 6–7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1–8, while only placebo marijuana was smoked on days 9–14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9–14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of ‘anxious’, ‘miserable’, ‘trouble sleeping’, ‘chills’, and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of ‘anxious’, ‘irritable’, ‘bad effect’, and ‘tired.’ Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

To conclude, there are currently no effective pharmacotherapies for cannabinoid dependence, yet the large number of nonresponders in marijuana treatment studies emphasizes the importance of increasing treatment options for marijuana dependence. We have developed a laboratory model to predict medications that may show promise clinically for the treatment of marijuana dependence. The present findings, in combination with earlier studies, suggest that nefazodone and oral THC show promise as potential treatment medications, while bupropion and divalproex do not…”

http://www.nature.com/npp/journal/v29/n1/full/1300310a.html

The cannabis withdrawal syndrome.

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Abstract

“PURPOSE OF REVIEW:

The demand for treatment for cannabis dependence has grown dramatically. The majority of the people who enter the treatment have difficulty in achieving and maintaining abstinence from cannabis. Understanding the impact of cannabis withdrawal syndrome on quit attempts is of obvious importance. Cannabis, however, has long been considered a ‘soft’ drug, and many continue to question whether one can truly become dependent on cannabis. Skepticism is typically focused on whether cannabis use can result in ‘physiological’ dependence or withdrawal, and whether withdrawal is of clinical importance.

RECENT FINDINGS:

The neurobiological basis for cannabis withdrawal has been established via discovery of an endogenous cannabinoid system, identification of cannabinoid receptors, and demonstrations of precipitated withdrawal with cannabinoid receptor antagonists. Laboratory studies have established the reliability, validity, and time course of a cannabis withdrawal syndrome and have begun to explore the effect of various medications on such withdrawal. Reports from clinical samples indicate that the syndrome is common among treatment seekers.

SUMMARY:

A clinically important withdrawal syndrome associated with cannabis dependence has been established. Additional research must determine how cannabis withdrawal affects cessation attempts and the best way to treat its symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/16612207

Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain.

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Image result for The Journal of Supportive Oncology

“Many patients with life-threatening diseases such as cancer experience severe symptoms that compromise their health status and deny them quality of life. Patients with cancer often experience cachexia, pain, and depression,which translate into an unacceptable quality of life. The discovery of the endocannabinoid system has led to a renewed interest in the use of cannabinoids for the management of nausea, vomiting, and weight loss arising either from cancer or the agents used to treat cancer. The endocannabinoid system has been found to be a key modulator of systems involved in pain perception, emesis, and reward pathways. As such, it represents a target for development of new medications for controlling the symptoms associated with cancer. Although the cannabinoid receptor agonist tetrahydrocannabinol and one of its analogs are currently the only agents approved for clinical use, efforts are under way to devise other strategies for activating the endocannabinoid system for therapeutic uses.”

http://www.ncbi.nlm.nih.gov/pubmed/15357514

The emerging role of cannabinoid neuromodulators in symptom management.

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Abstract

“INTRODUCTION:

The cannabinoids nabilone (Cesamet) and dronabinol (Marinol) are indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in cancer patients who have failed to respond adequately to conventional antiemetic therapy.

DISCUSSION:

The endocannabinoid (CB) system interacts with numerous other systems and pharmaceutical cannabinoids target ubiquitous CB1 and CB2 receptors in the central nervous system and periphery, relieving nausea and vomiting and pain.

SUMMARY:

The benefits of this novel class of medications in cancer may extend beyond CINV, as indicated by data from preclinical studies and animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/17139494

Ajulemic acid (IP-751): Synthesis, proof of principle, toxicity studies, and clinical trials

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Abstract

  “Ajulemic acid (CT-3, IP-751, 1′,1′-dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid) (AJA) has a cannabinoid-derived structure; however, there is no evidence that it produces psychotropic actions when given at therapeutic doses. In a variety of animal assays, AJA shows efficacy in models for pain and inflammation. Furthermore, in the rat adjuvant arthritis model, it displayed a remarkable action in preventing the destruction of inflamed joints. A phase-2 human trial with chronic, neuropathic pain patients suggested that AJA could become a useful drug for treating this condition. Its low toxicity, particularly its lack of ulcerogenicity, further suggests that it will have a highly favorable therapeutic index and may replace some of the current anti-inflammatory/analgesic medications. Studies to date indicate a unique mechanism of action for AJA that may explain its lack of adverse side effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751505/

The endocannabinoid system: a new molecular target for the treatment of tobacco addiction.

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Abstract

“Tobacco addiction is one of the leading preventable causes of mortality in the world and nicotine appears to be the main critical psychoactive component in establishing and maintaining tobacco dependence. Several lines of evidence suggest that the rewarding effects of nicotine, which underlie its abuse potential, can be modulated by manipulating the endocannabinoid system. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors reduces or eliminates many behavioral and neurochemical effects of nicotine that are related to its addictive potential. This review will focus on the recently published literature about the role of the endocannabinoid system in nicotine addiction and on the endocannabinoid system as a novel molecular target for the discovery of medications for tobacco dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/19128204

Endocannabinoid system involvement in brain reward processes related to drug abuse.

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“Cannabis is the most commonly abused illegal drug in the world and its main psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), produces rewarding effects in humans and non-human primates. Over the last several decades, an endogenous system comprised of cannabinoid receptors, endogenous ligands for these receptors and enzymes responsible for the synthesis and degradation of these endogenous cannabinoid ligands has been discovered and partly characterized. Experimental findings strongly suggest a major involvement of the endocannabinoid system in general brain reward functions and drug abuse. First, natural and synthetic cannabinoids and endocannabinoids can produce rewarding effects in humans and laboratory animals. Second, activation or blockade of the endogenous cannabinoid system has been shown to modulate the rewarding effects of non-cannabinoid psychoactive drugs. Third, most abused drugs alter brain levels of endocannabinoids in the brain. In addition to reward functions, the endocannabinoid cannabinoid system appears to be involved in the ability of drugs and drug-related cues to reinstate drug-seeking behavior in animal models of relapse. Altogether, evidence points to the endocannadinoid system as a promising target for the development of medications for the treatment of drug abuse.”

“The endogenous cannabinoid is a recently discovered system that appears to play an important and pervasive role in many types of drug abuse and dependence. Endogenous cannabinoids are neuromodulators that are involved in the signalling of rewarding events and can produce reinforcing and rewarding effects in experimental animals, as they do in humans. Endogenous cannabinoids can also activate other brain systems involved in reward signalling, can modulate the reinforcing and rewarding effects of other non-cannabinoid abused drugs, and are released by drugs of abuse in brain areas involved in reward and reinforcement processes. Accumulating evidence points to the endocannabinoid system as a major target for the development of new pharmacological agents for the treatment of many different types of drug abuse and dependence.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189556/

Cannabinoid CB1 Receptor Antagonists as Promising New Medications for Drug Dependence

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 “This review examines the development of cannabinoid CB1 receptor antagonists as a new class of therapeutic agents for drug addiction. Abused drugs [alcohol, opiates, Δ9-tetrahydrocannabinol (Δ9-THC), and psychostimulants, including nicotine] elicit a variety of chronically relapsing disorders by interacting with endogenous neural pathways in the brain. In particular, they share the common property of activating mesolimbic dopamine brain reward systems, and virtually all abused drugs elevate dopamine levels in the nucleus accumbens. Cannabinoid CB1 receptors are expressed in this brain reward circuit and modulate the dopamine-releasing effects of Δ9-THC and nicotine. Rimonabant (SR141716), a CB1 receptor antagonist, blocks both the dopamine-releasing and discriminative and rewarding effects of Δ9-THC in animals. Blockade of CB1 receptor activity by genetic invalidation also decreases rewarding effects of opiates and alcohol in animals. Although CB1 receptor blockade is generally ineffective in reducing the self-administration of cocaine in rodents and primates, it reduces the reinstatement of extinguished cocaine-seeking behavior produced by cocaine-associated conditioned stimuli and cocaine-priming injections. Likewise, CB1 receptor blockade is effective in reducing nicotine-seeking behavior induced by re-exposure to nicotine-associated stimuli. Some of these findings have been recently validated in humans. In clinical trials, Rimonabant blocks the subjective effects of Δ9-THC in humans and prevents relapse to smoking in exsmokers. Findings from both clinical and preclinical studies suggest that ligands blocking CB1 receptors offer a novel approach for patients suffering from drug dependence that may be efficacious across different classes of abused drugs.”

“Cannabinoid CB1 Receptor Blockade: A Step Forward in Drug-Dependence Therapy?”

“Despite advances in the understanding of neurobiological and behavioral mechanisms that lead to drug dependence over the last 20 years, no effective treatment is yet available for cocaine or Δ9-THC dependence. Moreover, medications available for ethanol, nicotine, or opioid dependence are ineffective in many subjects. For example, the rate of smoking cessation by subjects entering into clinical trials that combine effective medication and behavioral and cognitive therapy is around 30% at one year; most subjects relapse. Cannabinoid CB1 receptor antagonists represent a potentially useful tool not only for blocking the direct reinforcing effects of Δ9-THC, nicotine, and ethanol, but also for preventing relapse to the use of various drugs of abuse, including cocaine, methamphetamine, and heroin. In addition, environmental stimuli seem to be one of the major factors that can trigger relapse to drug use in abstinent drug abusers. This process is not only critical for psychostimulant abuse, but also for nicotine and heroin abuse, and probably for other drugs of abuse such as ethanol. By reducing the motivational effects of drug-related environmental stimuli, cannabinoid CB1 receptor antagonists might, therefore, provide an effective means for preventing relapse to drug-seeking behavior in abstinent drug abusers, providing a promising new tool for the treatment of dependence on a wide range of abused drugs.”

http://jpet.aspetjournals.org/content/312/3/875.long

Major Health Benefits of Medical Cannabis

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“The benefits of medical marijuana plant are extensive, pervasive, and long-standing. Because of the way the cannabis impacts the Autonomic Nervous System which develops the breath and relaxes the body, prospective for health and curative characteristics are huge. Some of the major health benefits of medical cannabis are explained below:

Treats Migraines

Cannabis healing has been very effective in the treatment of migraine headaches. Migraine headaches are vascular in source and are often preceded by an air characterized by nausea, flashes of light, faintness or photosensitivity.

Slows Down Tumor Growth

Studies have shown that cannabis help in slow down the facsimile and slow down the production of cancer cells in body. It is also a natural antiemetic, which makes it effectual in plummeting the nausea and vomiting related with chemo and radiation therapies. So taking marijuana slows down the tumor growth too.

Relieves Symptoms of Chronic Diseases

Marijuana is one of the best natural pain relievers that can help sufferers of chronic pain live more relaxed lives. The side effects are often much less severe than the other common pain medications.

Prevents Alzheimer’s

Cannabis reduces the occurrence of depression in Alzheimer’s patients, which can help patients to keep up a higher level of brain function. That is a powerful way to keep patients performance for a longer time after the first onset of Alzheimer’s disease.

Treats Glaucoma

Some strains of this medicinal plant have been shown that, they are potentially decreasing the force that glaucoma can place on the optic nerve; thereby the patients can easily cut the critical condition by smoking or taking the marijuana edibles or medicines.

Prevents Seizures

Seizure is a kind of epilepsy which almost affects more than 2 millions of Americans and 30 millions of people worldwide. Epilepsy is a condition when some of the brain cells become abnormally excitable. People using marijuana to control epilepsy should be alert when there is any removal of any tablets which controls seizures may leave you more susceptible to the patient. Marijuana is no exception. Patients with epilepsy are advised to exercise caution when using oral THC because there is no enough sufficient knowledge about the convulsive or anti-convulsive properties of the single compound.

For ADD and ADHD

Many people who endure with ADD and/or ADHD find that medical cannabis recovers their knack to hub and their level of recital with definite tasks. There are no clinical studies on humans but there are some beginner studies have done on animals that point to less hyperactivity and impulsivity with the use of cannabinoids (the active medicines in cannabis).

Relieve PMS

Millions of women have an illness on Premenstrual Syndrome (PMS). PMS includes the symptoms of headaches, abdominal cramps, bloating and fluid retention. Many women report that they have tried several different medications but none as give any significant relief like Medical Marijuana. Cannabis medicine has shown to give symptomatic relief from all the unpleasant symptoms of PMS.

Calm Those With Tourette’s and OCD

Several psychological disorders have been known to be related with the medical benefits of marijuana as well. Taking weed of prescribed amount on regular basis can slow down the tics for those who are suffering from Tourette’s syndrome and Obsessive Compulsive Disorder (OCD). Yes some of the qualities in marijuana plant help the patient to calm themselves when any creation of intrusive thoughts which produces fear, uneasiness and abnormal behaviors.”

http://www.herbalmission.org/major-health-benefits-of-medical-cannabis.php

Targeted modulators of the endogenous cannabinoid system: future medications to treat addiction disorders and obesity.

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Abstract

“The endogenous endocannabinoid system encompasses a family of natural signaling lipids (“endocannabinoids”) functionally related to (9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (cannabis), along with proteins that modulate the endocannabinoids, including enzymes, transporters, and receptors. The endocannabinoid system’s ubiquitous regulatory actions in health and disease underscore its importance to mammalian (patho)physiology and suggest discrete targets through which it may be modulated for therapeutic gain. Medications based on the endocannabinoid system are an important focus of contemporary translational research, particularly with respect to substance abuse and obesity, two prevalent disorders with a pathogenic component of endocannabinoid system hyperactivity. Pressing health care needs have made the rational design of targeted CB1 cannabinoid-receptor modulators a promising route to future medications with significant therapeutic impact against psychobehavioral and metabolic disturbances having a reward-supported appetitive component.”

http://www.ncbi.nlm.nih.gov/pubmed/17915075