“Twenty-eight states in the U.S have legalized medical marijuana, yet its impacts on severe health consequences such as hospitalizations remain unknown. Meanwhile, the prevalence of opioid pain reliever (OPR) use and outcomes has increased dramatically. Recent studies suggested unintended impacts of legalizing medical marijuana on OPR, but the evidence is still limited. This study examined the associations between state medical marijuana policies and hospitalizations related to marijuana and OPR.
Category Archives: Addiction
Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders.
“Learning to associate cues or contexts with potential threats or rewards is adaptive and enhances survival. Both aversive and appetitive memories are therefore powerful drivers of behaviour but the inappropriate expression of conditioned responding to fear- and drug-related stimuli can develop into anxiety-related and substance abuse disorders, respectively. These disorders are associated with abnormally persistent emotional memories and inadequate treatment, often leading to symptom relapse.
Studies show that cannabidiol, the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, reduces anxiety via serotonin1A and (indirect) cannabinoid receptor activation in paradigms assessing innate responses to threat.
Accumulating evidence from animal studies investigating the effects of cannabidiol on fear memory processing also indicates that it reduces learned fear in paradigms that are translationally relevant to phobias and post-traumatic stress disorder.
Cannabidiol does so by reducing fear expression acutely, and by disrupting fear memory reconsolidation and enhancing fear extinction, both of which can result in the lasting reduction of learned fear.
Recent studies have also begun to determine the effects of cannabidiol on drug memory expression using paradigms with translational relevance to addiction. Emerging evidence suggests that cannabidiol reduces the expression of drug memories acutely and by disrupting their reconsolidation.
Here we review the literature demonstrating the anxiolytic effects of cannabidiol before focusing on studies investigating its effects on various fear and drug memory processes. Understanding how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use in treating anxiety-related and substance abuse disorders.”
Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation.
“Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes.
Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior.
In conclusion, rats exposed to adolescent intermittent alcohol displayed anxiety-like behavior and cognitive deficits in adulthood and these alterations were accompanied by brain region-dependent changes in the gene expression of the ECS and other signals associated with neuroinflammation and behavior.
An intermittent adolescent alcohol exposure has behavioral and molecular consequences in the adult brain, which might be linked to higher vulnerability to addictive behaviors and psychopathologies.”
Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice.
“Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood.
The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed.
Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy.
The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis.
We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS.” https://www.ncbi.nlm.nih.gov/pubmed/28220044
“Pregnenolone can protect the brain from cannabis intoxication. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/
Brain cannabinoid CB₂ receptors modulate cocaine’s actions in mice.
“These findings, for the first time, suggest that brain CB2 receptors modulate cocaine’s rewarding and locomotor-stimulating effects, likely by a DA-dependent mechanism.
Whatever the mechanisms, the present findings, for the first time, suggest that activation of brain CB2 receptors inhibits cocaine’s rewarding and psychomotor-stimulating effects, which is congruent with a rapidly expanding corpus of published reports implicating brain CB2 receptors in modulating a variety of CNS functions such as locomotion, pain, emesis, neurogenesis, and neuroprotection.
This finding not only challenges current views that CB2 receptors are absent from the CNS and that CB2 receptor ligands lack CNS effects, but also suggests that brain CB2 receptors may be a novel target for the pharmacotherapy of drug abuse and addiction.” http://europepmc.org/articles/pmc3164946
“Marijuana Could be Used to Treat Cocaine Addiction, According to Federal Research” http://www.laweekly.com/news/marijuana-could-be-used-to-treat-cocaine-addiction-according-to-federal-research-2392363
Cannabidiol reduces ethanol consumption, motivation and relapse in mice.
“This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice.
Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol.
These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/28194850
Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.
“Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated.
Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived rats.
These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.”
https://www.ncbi.nlm.nih.gov/pubmed/19553915
“The surprising effect of cannabis on morphine dependence. Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth.” https://medicalxpress.com/news/2009-07-effect-cannabis-morphine.html
“THC HELPS LAB RATS KICK THE MORPHINE HABIT” http://hightimes.com/medicinal/thc-helps-lab-rats-kick-the-morphine-habit/
Differential Expression of Endocannabinoid System-Related Genes in the Dorsal Hippocampus following Expression and Reinstatement of Morphine Conditioned Place Preference in Mice.
“The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine.
Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation. To test this possibility, we systematically compared the expression of eCB-related genes in the dorsal hippocampus following the expression, extinction, and reinstatement of morphine CPP using quantitative RT-PCR analyses.
These results suggest that differential regulation of the synthesis and/or degradation of the eCB system contribute to the expression and reinstatement of morphine CPP.”
Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic.
“Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.”
Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.
“This study assessed whether oral administration of delta-9-tetrahydrocannbinol (THC) effectively suppressed cannabis withdrawal in an outpatient environment.
The primary aims were to establish the pharmacological specificity of the withdrawal syndrome and to obtain information relevant to determining the potential use of THC to assist in the treatment of cannabis dependence.
METHOD:
Eight adult, daily cannabis users who were not seeking treatment participated in a 40-day, within-subject ABACAD study. Participants administered daily doses of placebo, 30 mg (10 mg/tid), or 90 mg (30 mg/tid) oral THC during three, 5-day periods of abstinence from cannabis use separated by 7-9 periods of smoking cannabis as usual.
RESULTS:
Comparison of withdrawal symptoms across conditions indicated that (1) the lower dose of THC reduced withdrawal discomfort, and (2) the higher dose produced additional suppression in withdrawal symptoms such that symptom ratings did not differ from the smoking-as-usual conditions. Minimal adverse effects were associated with either active dose of THC.
CONCLUSIONS:
This demonstration of dose-responsivity replicates and extends prior findings of the pharmacological specificity of the cannabis withdrawal syndrome. The efficacy of these doses for suppressing cannabis withdrawal suggests oral THC might be used as an intervention to aid cannabis cessation attempts.” https://www.ncbi.nlm.nih.gov/pubmed/16769180
“The endocannabinoid system as a target for the treatment of cannabis dependence” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647947/
“Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. CBD can be effective for the treatment of cannabis withdrawal syndrome.” https://www.ncbi.nlm.nih.gov/pubmed/23095052
“Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.” https://www.ncbi.nlm.nih.gov/pubmed/16769180