Category Archives: Addiction
Ventilatory-depressant effects of opioids alone and in combination with cannabinoids in rhesus monkeys.
“Pain is a serious health problem that is commonly treated with opioids, although the doses of opioids needed to treat pain are often similar to those that decrease respiration. Combining opioids with drugs that relieve pain through non-opioid mechanisms can decrease the doses of opioids needed for analgesia, resulting in an improved therapeutic window, but only if the doses of opioids that decrease respiration are not similarly decreased. Using small doses of opioids to treat pain has the potential to reduce the number of overdoses and deaths.
This study investigated whether the cannabinoid receptor agonists Δ9-tetrahydrocannabinol (Δ9-THC) and CP 55,940 modify the ventilatory-depressant effects of morphine and fentanyl in three monkeys.
In summary, cannabinoid receptor agonists, which increase the potency of opioids to produce antinociception, did not increase their potency to depress ventilation. Thus, the therapeutic window is greater for opioids when they are combined with cannabinoid receptor agonists, indicating a possible advantage for these drug mixtures in treating pain.”
https://www.ncbi.nlm.nih.gov/pubmed/29807027
https://www.sciencedirect.com/science/article/pii/S0014299918303108
Computational investigation on the binding modes of Rimonabant analogues with CB1 and CB2.
“The human cannabinoid G protein coupled receptor 1 (CB1) is highly expressed in central nervous system. CB1-selective antagonists show therapeutic promise in a wide range of disorders, such as obesity-related metabolic disorders, dyslipidemia, drug abuse and type 2 diabetes. Rimonabant (SR141716A), MJ08 and MJ15 are selective CB1 antagonists with selectivity >1000 folds over CB2 despite of 42% sequence identity between CB1 and CB2. The integration of homology modeling, automated molecular docking and molecular dynamics simulation were used to investigate the binding modes of these selective inverse agonists/antagonists with CB1 and CB2 and their selectivity. Our analyses showed that the hydrophobic interactions between ligands and hydrophobic pockets of CB1 account for the main binding affinity. In addition, instead of interacting with ligands directly as previously reported, the Lys1923.28in CB1 was engaged in indirect interactions with ligands to keep inactive-state CB1 stable by forming the salt bridge with Asp1762.63 . Lastly, our analyses indicated that the selectivity of these antagonists came from the difference in geometry shapes of binding pockets of CB1 and CB2. The present study could guide future experimental works on these receptors and has the guiding significance for the design of functionally selective drugs targeting CB1 or CB2 receptors.” https://www.ncbi.nlm.nih.gov/pubmed/29797785 https://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.13337]]>
Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.
“The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches.
This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids).”
https://www.ncbi.nlm.nih.gov/pubmed/29776349 “There is a need for more effective treatment approaches for cannabis dependent patients who are unable to discontinue their illicit use through psychosocial interventions alone. Longer-term agonist replacement treatment approaches rather than acute withdrawal management are likely to be more effective, with the combination of THC:CBD nabiximols preparation being potentially advantageous over synthetic THC analogues. This is the first large-scale outpatient RCT of nabiximols for this population, and has required the development of clinical and research methods specific to agonist treatment with a plant-derived cannabinoid formulation, building upon clinical research models previously used in opioid agonist treatment approaches.” https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-018-1682-2]]>Effects of exercise on experimentally manipulated craving for cannabis: A preliminary study.
“Cannabis is the most commonly used illicit drug in the United States, and craving for cannabis is related to cannabis use.
Exercise has been demonstrated to reduce craving for substances.
The findings suggest that moderate exercise may be useful for reducing craving, particularly among those who use larger quantities of cannabis.”
https://www.ncbi.nlm.nih.gov/pubmed/29792472
“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.