Category Archives: Addiction

Curing addiction with cannabis medicines

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“Smokers trying to quit in the future could do it with the help of cannabis based medicines, according to research from The University of Nottingham.

Teams of pharmacologists, studying the cannabis-like compounds which exist naturally in our bodies (endocannabinoids), are exploring the potential for medical treatment. This includes treating conditions as diverse as obesity, diabetes, depression and addiction to substances like nicotine.

Scientists have known about endocannabinoids since the mid-1990s. This led to an explosion in the number of researchers looking into the future medical uses of cannabinoids and cannabis compounds.

Dr Steve Alexander, Associate Professor in the School of Biomedical Sciences, focused on a number of these projects in editing the first themed podcast for the British Journal of Pharmacology.

Dr Alexander said: “It is clear that there is very realistic potential for cannabinoids as medicines. Scientists are looking at a range of possible applications.”

One of these researchers is Professor David Kendall, a cellular pharmacologist at the University: “The brain is full of cannabinoid receptors. And so, not surprisingly with diseases like depression and anxiety, there’s a great deal of interest in exploiting these receptors and in doing so, developing anti-depressant compounds.”

Addiction is a real target – researchers like Professor Kendall believe the endocannabinoids could be a crucial link to addictive behaviour: “We know that the endocannabinoid system is intimately involved in reward pathways and drug seeking behaviour. So this tends to indicate that that if the link involving endocannabinoids and the reward pathway, using inhibitors, can be interrupted, it could turn down the drive to seek addictive agents like nicotine.”

Because cannabinoids have also been shown to bring down blood pressure, it is hoped that related compounds can be used in patients with conditions like hypertension.

Dr Michael Randall, a cardiovascular pharmacologist at the University has looked at how endocannabinoids cause blood vessels to relax. “This could have many implications,” Dr Randall said. “The endocannabinoids appear to lower blood pressure under certain conditions; states of shock for example. If the endocannabinoids are of physiological importance, this could have real therapeutic possibilities.”

“In terms of getting better medicines the endocannabinoid system has a lot to offer,” said Dr Alexander. “The range of cannabis-related medicines is currently limited, but by increasing our knowledge in this area we can increase our stock.”

The University of Nottingham”

http://www.brightsurf.com/news/headlines/36296/Curing_addiction_with_cannabis_medicines.html

Medical Marijuana as Treatment for Alcoholism & Addiction

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“Medical marijuana is frequently in the news, and hopefully the growing awareness of the benefits of medical marijuana will lead to more sensible regulations and deeper research into why cannabis is so helpful in treating so many different conditions. Among the conditions that medical marijuana can treatis addiction, whether to drugs or alcohol.”

“Medical Marijuana as a Recovery Treatment”

“Marijuana as a recovery treatment is controversial, not least because there is conflicting research about whether medical marijuana is or is not addictive. However, many studies have found that medical marijuana is not addictive, or as harmful, as other drugs such as alcohol and opiates. Additionally, several studies have shown that marijuana can be an effective treatment for recovery from other substances.”

Read more: http://www.unitedpatientsgroup.com/blog/2012/07/26/medical-marijuana-as-treatment-for-alcoholism-addiction/

Marijuana To Control Alcohol Abuse

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By Senior News Editor
Reviewed by John M. Grohol, Psy.D. on December 1, 2009

New Strategy Uses Pot To Control Alcohol Abuse “A new research effort has a provocative outcome as University of California-Berkeley researchers suggest substituting cannabis for treatment of heavy alcohol abuse.

Research published in BioMed Central’s open access Harm Reduction Journal features a poll of 350 cannabis users, finding that 40 percent used cannabis to control their alcohol cravings, 66 percent as a replacement for prescription drugs and 26 percent for other, more potent illegal drugs.

Amanda Reiman carried out the study at the UC-Berkeley Patient’s Group, a medical cannabis dispensary.

She said, “Substituting cannabis for alcohol has been described as a radical alcohol treatment protocol. This approach could be used to address heavy alcohol use in the British Isles – people might substitute cannabis, a potentially safer drug than alcohol with less negative side effects, if it were socially acceptable and available.”

Reiman found that 65 percent of people reported using cannabis as a substitute because it has fewer adverse side effects than alcohol, illicit or prescription drugs, 34 percent because it has less withdrawal potential and 57.4 percent because cannabis provides better symptom management.

Reiman believes this discovery brings up two important points.

“First, self-determination, the right of an individual to decide which treatment or substance is most effective and least harmful for them. Secondly, the recognition that substitution might be a viable alternative to abstinence for those who can’t or won’t completely stop using psychoactive substances.”

Speaking about legalization of cannabis, Reiman added, “The economic hardship of the Great Depression helped bring about the end of alcohol prohibition. Now, as we are again faced with economic struggles, the U.S. is looking to marijuana as a potential revenue generator.

“Public support is rising for the legalization of recreational use and remains high for the use of marijuana as a medicine. The hope is that this interest will translate into increased research support and the removal of current barriers to conducting such research, such as the Schedule I/Class B status of marijuana.””

http://psychcentral.com/news/2009/12/01/marijuana-to-control-alcohol-abuse/9863.html

Involvement of the endogenous cannabinoid system in the effects of alcohol in the mesolimbic reward circuit: electrophysiological evidence in vivo.

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Abstract

“RATIONALE:

Several lines of evidence indicate that the endogenous cannabinoid system is involved in the pharmacological and behavioural effects of alcohol. The mesolimbic dopaminergic (DA) system and the nucleus accumbens (NAc) process rewarding properties of drugs of abuse, including alcohol and cannabinoids, whereas endocannabinoids in these regions modulate synaptic function and mediate short- and long-term forms of synaptic plasticity.

OBJECTIVES:

The present study was designed to investigate the contribution of the endogenous cannabinoid system in alcohol electrophysiological effects in the mesolimbic reward circuit.

METHODS:

We utilized extracellular single cell recordings from ventral tegmental area (VTA) DA and NAc neurons in anesthetized rats. DA neurons were antidromically identified as projecting to the shell of NAc, whereas NAc putative medium spiny neurons were identified by their evoked responses to basolateral amygdala (BLA) stimulation.

RESULTS:

Alcohol stimulated firing rate of VTA DA neurons and inhibited BLA-evoked NAc neuron spiking responses. The cannabinoid type-1 receptor (CB1) antagonist rimonabant (SR141716A) fully antagonized alcohol effect in both regions. In the NAc, either inhibition of the major catabolic enzyme of the endocannabinoid anandamide, the fatty-acid amyd hydrolase, with URB597 or a pretreatment with the CB1 receptor agonist WIN55212-2 significantly depressed alcohol-induced effects in the NAc.

CONCLUSIONS:

These results corroborate the notion of the involvement of endocannabinoids and their receptors in the actions of alcohol and highlight the endocannabinoid system as a valuable target in the therapy for alcoholism.”

http://www.ncbi.nlm.nih.gov/pubmed/16228194

Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans.

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Abstract

“We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. Mice experiencing more alcohol preference by drinking showed reduced Cb2 gene expression, whereas mice with little preference showed no changes of it in ventral midbrain. Alcohol preference in conjunction with chronic mild stress were enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic stress, whereas antagonist AM630 prevented development of alcohol preference. There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population (P=0.007; odds ratio 1.25, 95% CI, (1.06-1.47)). CB2 under such environment is associated with the physiologic effects of alcohol and CB2 antagonists may have potential as therapies for alcoholism.”

http://www.ncbi.nlm.nih.gov/pubmed/17189959

Blockade of the cannabinoid CB1 receptor and alcohol dependence: preclinical evidence and preliminary clinical data.

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Abstract

“The present paper summarizes the results of a number of pharmacological studies implicating the cannabinoid CB(1) receptor in the neural circuitry regulating different alcohol-related behaviors in rodents. Specifically, cannabinoid CB(1) receptor antagonists–including the prototype, rimonabant–have been reported to suppress: (a) acquisition and maintenance of alcohol drinking behavior under the 2-bottle “alcohol vs water” choice regimen; (b) the increase in alcohol intake occurring after a period of alcohol abstinence (an experimental model of alcohol relapse); (c) alcohol’s reinforcing and motivational properties measured in rats trained to perform a specific task (e.g., lever-pressing) to access alcohol; (d) reinstatement of extinguished alcohol-seeking behavior triggered in rats by a nicotine challenge or presentation of cues previously associated to alcohol availability (another model of alcohol relapse). Additional data indicate that the opioid receptor antagonists, naloxone and naltrexone, synergistically potentiate the suppressing effect of rimonabant on alcohol intake and alcohol’s motivational properties in rats. Conversely, the two clinical studies conducted to date (one in alcohol-dependent individuals and one in nontreatment-seeking heavy alcohol drinkers) yielded less conclusive results. Unfortunately, the recent discontinuation–due to the occurrence of some psychiatric adverse effects–of all trials with cannabinoid CB(1) receptor antagonists apparently hinders further investigations on the potential of rimonabant in the treatment of alcohol dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/20201816

Cannabinoid receptor 1 blocker rimonabant (SR 141716) for treatment of alcohol dependence: results from a placebo-controlled, double-blind trial.

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Abstract

“Multiple lines of evidence suggest that the endocannabinoid system is implicated in the development of alcohol dependence. In addition, in animal models, the cannabinoid receptor 1 blocker rimonabant was found to decrease alcohol consumption, possibly by indirect modulation of dopaminergic neurotransmission. This was a 12-week double-blind, placebo-controlled, proof-of-concept study to assess the possible efficacy of the cannabinoid receptor 1 antagonist rimonabant 20 mg/d (2 x 10 mg) in the prevention of relapse to alcohol in recently detoxified alcohol-dependent patients. A total of 260 patients were included, 258 were exposed to medication, and 208 (80.6%) were men. Patients had an alcohol history of 15 years on average. More patients in the rimonabant group (94/131 [71.8%]) completed treatment compared with the placebo group (79/127 [62.2%]). Although there was a modest effect of rimonabant with respect to relapse rate, there were no statistically significant differences between treatment groups. Approximately 41.5% of the rimonabant group had relapsed to drinking at the end of the study compared with 47.7% of the placebo group (obtained from Kaplan-Meier-curve). Differences were more marked but not statistically significant in patients who relapsed to heavy drinking: 27.7% versus 35.6%, respectively. Safety and tolerance of the drug were good. Similar rates of adverse events were reported between the 2 groups; less patients experienced serious events or discontinued the treatment with rimonabant compared with placebo. Rates of depression-related events were low (3.8% with rimonabant compared with 1.6% with placebo). Patients on rimonabant lost weight (Mean, -1.7 kg) compared with baseline, whereas there was no such change in the placebo group. Weight loss was more pronounced in patients with a higher body mass index. In addition, there was a significant decrease in leptin levels in the rimonabant group compared with baseline. Lack of efficacy in this study may be explained by a very high response rate in the placebo group and a relatively short treatment duration. Taking the substantial numbers of animal studies suggesting a possible role of CB1 antagonists for the treatment of alcohol dependence into account, it seems worthwhile to further test cannabinoid blockers in the treatment of alcoholism.”

http://www.ncbi.nlm.nih.gov/pubmed/18480689

Positron Emission Tomography Shows Elevated Cannabinoid CB (1) Receptor Binding in Men with Alcohol Dependence.

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Abstract

“BACKGROUND:

Several lines of evidence link cannabinoid (CB) type 1 (CB (1) ) receptor-mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB (1) receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD.”

 

“CONCLUSIONS:

These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB (1) receptors in AD. The current study design does not answer the important question of whether elevated CB (1) receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.”

http://www.ncbi.nlm.nih.gov/pubmed/22551199

Reduced cannabinoid CB(1) receptor binding in alcohol dependence measured with positron emission tomography.

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Abstract

“Brain cannabinoid CB(1) receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB(1) receptors in alcohol dependent patients in early and protracted abstinence, and in comparison with control subjects without alcohol use disorders, using positron emission tomography and [(18)F]FMPEP-d(2), a radioligand for CB(1) receptors. We scanned 18 male in-patients with alcohol dependence twice, within 3-7 days of admission from ongoing drinking, and after 2-4 weeks of supervised abstinence. Imaging data were compared with those from 19 age-matched healthy male control subjects. Data were also analyzed for potential influence of a common functional variation (rs2023239) in the CB(1) receptor gene (CNR1) that may moderate CB(1) receptor density. On the first scan, CB(1) receptor binding was 20-30% lower in patients with alcohol dependence than in control subjects in all brain regions and was negatively correlated with years of alcohol abuse. After 2-4 weeks of abstinence, CB(1) receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB(1) receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB(1) receptor binding in the human brain and this reduction persists at least 2-4 weeks into abstinence. The correlation of reduced binding with years of alcohol abuse suggests an involvement of CB(1) receptors in alcohol dependence in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/22776901

A Critical Role for the Cannabinoid CB1 Receptors in Alcohol Dependence and Stress-Stimulated Ethanol Drinking

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“Although many people drink alcohol regularly, only some become addicted. Several studies have shown that genetic and environmental factors contribute to individual differences in the vulnerability to the effects of alcohol. Among the environmental factors, stress is perhaps the most important trigger for relapse after a period of abstinence. Here we show that ethanol withdrawal symptoms were completely absent in cannabinoid CB1 receptor-deficient mice, although acute effects of ethanol and ethanol tolerance and preference were basically normal. Furthermore, foot-shock stress had no affect on alcohol preference in Cnr1−/− mice, although it induced a dramatic increase in Cnr1+/+ animals. These results reveal a critical role for the CB1 receptor in clinically important aspects of alcohol dependence and provide a rationale for the use of CB1 receptor antagonists in the treatment of alcohol addiction.”

“In summary, the endocannabinoid system does not seem to be crucial for the rewarding effects of ethanol and the manifestation of normal ethanol drinking behaviors. However, it appears to play an important role in the manifestation of stress-induced alcohol drinking and ethanol withdrawal. These results support the notion that the neuronal mechanisms involved in drug reinforcement are dissociable from those involved in withdrawal and reinstatement. Indeed, our results demonstrate that ethanol tolerance and physical dependence can be separated. Thus, CB1 receptor antagonists may be useful for the treatment of alcohol addiction.”

http://www.jneurosci.org/content/23/6/2453.long