“Morphine is a potent opioid analgesic used to alleviate moderate or severe pain but the development of drug tolerance and dependence limits its use in pain management. Previous studies showed that cannabinoid type 2 (CB2) receptor ligands may modulate opioid effects. However, there is no report of the effect of CB2 receptor agonist on acute morphine tolerance and physical dependence. We therefore investigated the effect of a CB2 receptor agonist (AM1241) on morphine-induced morphine tolerance and physical dependence in mice. Our findings suggest that coadministration of the CB2 receptor agonist and morphine could increase morphine antinociception and reduce morphine tolerance and physical dependence in mice.
Category Archives: Addiction
Cannabinoid-Opioid Interaction in Chronic Pain
“Cannabis inhalation with a vaporizer may enhance the analgesia of opioids.
In addition, previous research suggest that Cannabis may be useful in attenuating the development of opioid tolerance and dependence.
This is the first human study to show that inhaled cannabis safely potentiates the analgesia of opioids.
HUMAN STUDY SHOWS INHALED CANNABIS POTENTIATES ANALGESIA OF OPIOIDS.”
https://www.naturalmedicinejournal.com/journal/2012-06/cannabinoid-opioid-interaction-chronic-pain ]]>Antinociceptive Synergy between 9 -Tetrahydrocannabinol and Opioids after Oral Administration
“Cannabinoids and opioids have been shown to possess several similar pharmacological effects, including analgesia The analgesic effects of opioids, such as morphine and codeine, in mice are enhanced by oral administration of the cannabinoid 9 -tetrahydrocannabinol (9 -THC). These findings suggest that the use of a low-dose combination of analgesics is a valid and effective approach for the treatment of pain and necessitates further study. In summary, we have observed that 9 -THC enhances the antinociceptive effects of morphine and codeine in a synergistic fashion. This is the first report of a true synergistic interaction between oral 9 -THC and morphine or codeine, since previous studies have only examined one-dose combinations. Much more work needs to be done to elucidate the mechanisms by which cannabinoids and opioids interact to produce analgesia. However, the implication that a combination of drugs may be more effective than either drug alone, and at the same time possibly reduce the occurrence of side effects, should provoke further study on analgesic drug interactions.” http://jpet.aspetjournals.org/content/jpet/304/3/1010.full.pdf http://healthdocbox.com/Substance_Abuse/71109245-Antinociceptive-synergy-between-9-tetrahydrocannabinol-and-opioids-after-oral-administration.html]]>
Molecular and cellular basis of cannabinoid and opioid interactions.
“Cannabinoids and opioids have been shown to possess several similar pharmacological effects, including analgesia and stimulation of brain circuitry that are believed to underlie drug addiction and reward. In recent years, these phenomena have supported the possible existence of functional links in the mechanisms of action of both types of drugs.
The present review addresses the recent advances in the study of biochemical and molecular mechanisms underlying opioid and cannabinoid interaction. Several hypothesis have been formulated to explain this cross-modulation including the release of opioid peptides by cannabinoids or endocannabinoids by opioids and interaction at the level of receptor and/or their signal transduction mechanisms.
Moreover it is important to consider that the nature of cannabinoid and opioid interaction might differ in the brain circuits mediating reward and in those mediating other pharmacological properties, such as antinociception.
Further studies are needed since a better knowledge of the opioid-cannabinoid interaction may lead to exciting therapeutic possibilities.”
https://www.ncbi.nlm.nih.gov/pubmed/15927245
https://www.sciencedirect.com/science/article/pii/S0091305705001450?via%3Dihub
Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.
“Cannabidiol (CBD), a non-intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side-effects and research showing it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side-effects.
FINDINGS:
When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.CONCLUSIONS:
A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.” https://www.ncbi.nlm.nih.gov/pubmed/29714034 https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14243“Cannabidiol reduces attentional bias to cigarette cues in nicotine addicts, study finds” http://www.psypost.org/2018/06/cannabidiol-reduces-attentional-bias-cigarette-cues-nicotine-addicts-study-finds-51351
]]>The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.
“There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users.
CONCLUSIONS:
Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders.” https://www.ncbi.nlm.nih.gov/pubmed/29689485 https://www.drugandalcoholdependence.com/article/S0376-8716(18)30184-4/fulltext]]>Testing associations between cannabis use and subcortical volumes in two large population-based samples.
“Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi-substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes.
FINDINGS:
After correcting for multiple testing (p=0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle-age males.CONCLUSIONS:
In exploratory analyses based on young adult and middle age samples, normal variation in cannabis use is statistically unrelated to individual differences in brain morphology as measured by subcortical volume.” https://www.ncbi.nlm.nih.gov/pubmed/29691937 https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14252]]>Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.
“Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.
Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen’s d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.
Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”
“The decision to authorize a patient for continued enrollment in a state-sanctioned medical