CB₁ receptor antagonism in the bed nucleus of the stria terminalis interferes with affective opioid withdrawal in rats.

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“The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region.

Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning.

The current findings emphasize an important role for the BNST in opioid withdrawal and suggest that the ameliorative effects of systemically administered CB1 antagonists are mediated, in part, by their actions within this region.”

https://www.ncbi.nlm.nih.gov/pubmed/28714716

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report

“Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain.

The results of this study provide implications from both a micro and macro level. First, from the macro level, there have been three previously published indicators of public health changes in states that permit medical cannabis: decreases in opioid related mortality, decreases in spending on opioids, and a decrease in traffic fatalities. While none of these studies shows a cause and effect relationship, they do suggest public health related population based changes in localities where cannabis can be accessed to treat pain. Given that the participants in this study reported a greater likelihood of using cannabis as a substitute in a less stigmatized and easily accessible environment, it makes sense why we would see these changes in locations where medical cannabis is sanctioned versus places where it is illegal.

At the micro level, there is a great deal of individual risk associated with prolonged use of opioids and perhaps even nonopioid-based pain medications. The prescribing of opioids has not been curbed in the United States, despite the growing number of fatal overdoses and reported dependence. Providing the patient with the option of cannabis as a method of pain treatment alongside the option of opioids might assist with pain relief in a safer environment with less risk. A society with less opioid dependent people will result in fewer public health harms.”

http://online.liebertpub.com/doi/10.1089/can.2017.0012

Cannabinoids could make opioids more effective, meaning pain relief with lower doses and reduced risk of dependency

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“In animal studies, four times less morphine and ten times less codeine was needed when cannabinoids were given at the same time.

The higher the dose of opioid pain relievers, the more likely it is a patient will experience side effects and complications. With the opioid epidemic becoming a pressing problem, researchers are working to find ways to provide pain relief with less risk. To understand whether therapeutic cannabinoids could be an effective strategy to reduce opioid use, researchers at the University of New South Wales and the Centre for Addiction and Mental Health analysed data from 19 pre-clinical studies and nine clinical trials.

“These studies highlight the potential beneficial effects of combining opioids and cannabinoids””

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain

 

409715“To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain.

Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC.”

https://academic.oup.com/painmedicine/article-abstract/18/2/294/2924709/Problematic-Use-of-Prescription-Opioids-and?redirectedFrom=fulltext

The endocannabinoid system as a target for addiction treatment: Trials and tribulations.

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“Addiction remains a major public health concern, and while pharmacotherapies can be effective, clinicians are limited by the paucity of existing interventions. Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction.

Current evidence suggests that pharmacotherapies containing delta-9-tetrahydrocannabinol, such as dronabinol and nabiximols, are effective for cannabis withdrawal. Dronabinol may also reduce symptoms of opioid withdrawal. The cannabinoid receptor 1 (CB1) inverse agonist rimonabant showed promising effects for smoking cessation but also caused psychiatric side effects and currently lacks regulatory approval. Few trials have investigated cannabinergic medications for alcohol use disorder.

Overall, the endocannabinoid system remains a promising target for addiction treatment. Development of novel medications such as fatty acid amide hydrolase inhibitors and neutral CB1 antagonists promises to extend the range of available interventions.”

https://www.ncbi.nlm.nih.gov/pubmed/28564576

http://www.sciencedirect.com/science/article/pii/S0028390817302563

Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.

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“Cannabinoid pharmacology has been intensely studied because of cannabis’ pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. The identification of allosteric modulators of the cannabinoid receptor 1 (CB1) has given a new direction to the development of cannabinoid-based therapeutics due to the many advantages offered by targeting allosteric site(s). Allosteric receptor modulators hold potential to develop subtype-specific and pathway-specific therapeutics. Here we briefly discuss the first-generation of allosteric modulators of CB1 receptor, their structure-activity relationships, signaling pathways and the allosteric binding site(s) on the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/28527758

http://www.sciencedirect.com/science/article/pii/S0028390817302307

Cannabis as a substitute for prescription drugs – a cross-sectional study

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“The use of medical cannabis is increasing, most commonly for pain, anxiety and depression. Emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal. The aim of this study was to survey cannabis users to determine whether they had intentionally substituted cannabis for prescription drugs.

A total of 1,248 (46%) respondents reported using cannabis as a substitute for prescription drugs. The most common classes of drugs substituted were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%) and antidepressants (12.7%). A total of 2,473 substitutions were reported or approximately two drug substitutions per affirmative respondent.

These patient-reported outcomes support prior research that individuals are using cannabis as a substitute for prescription drugs, particularly, narcotics/opioids, and independent of whether they identify themselves as medical or non-medical users. This is especially true if they suffer from pain, anxiety and depression. Additionally, this study suggests that state laws allowing access to, and use of, medical cannabis may not be influencing individual decision-making in this area.”

https://www.dovepress.com/cannabis-as-a-substitute-for-prescription-drugs-ndash-a-cross-sectiona-peer-reviewed-article-JPR

Intentional cannabis use to reduce crack cocaine use in a Canadian setting: A longitudinal analysis.

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“No effective pharmacotherapies exist for the treatment of crack cocaine use disorders. Emerging data suggests that cannabinoids may play a role in reducing cocaine-related craving symptoms. This study investigated the intentional use of cannabis to reduce crack use among people who use illicit drugs (PWUD).

A period of intentional cannabis use to reduce crack use was associated with decreased frequency of crack use in subsequent periods among PWUD.”

https://www.ncbi.nlm.nih.gov/pubmed/28399488

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep.

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“A prior epidemiological study identified a reduction in opioid overdose deaths in US states that legalized medical cannabis (MC). One theory to explain this phenomenon is a potential substitution effect of MC for opioids. This study evaluated whether this substitution effect of MC for opioids also applies to other psychoactive medications.

New England dispensary members ( n = 1,513) completed an online survey about their medical history and MC experiences. Among respondents that regularly used opioids, over three-quarters (76.7%) indicated that they reduced their use since they started MC. This was significantly ( p < 0.0001) greater than the patients that reduced their use of antidepressants (37.6%) or alcohol (42.0%). Approximately two-thirds of patients decreased their use of anti-anxiety (71.8%), migraine (66.7%), and sleep (65.2%) medications following MC which significantly ( p < 0.0001) exceeded the reduction in antidepressants or alcohol use. The patient’s spouse, family, and other friends were more likely to know about their MC use than was their primary care provider.

In conclusion, a majority of patients reported using less opioids as well as fewer medications to treat anxiety, migraines, and sleep after initiating MC. A smaller portion used less antidepressants or alcohol. Additional research is needed to corroborate these self-reported, retrospective, cross-sectional findings using other data sources.”

https://www.ncbi.nlm.nih.gov/pubmed/28372506

Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice.

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“CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine.

Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine.

Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse.”

https://www.ncbi.nlm.nih.gov/pubmed/28366798