Page 11 - JCTR-11-1

Journal of Clinical and
Translational Research Cannabinoids for cannabis use disorder

consequences, including the development of cannabis use has been linked to increased adenylyl cyclase activity in the
disorder (CUD). 2 cerebellum, which contrasts with the acute effects of CBs
As outlined in the Diagnostic and Statistical Manual that typically inhibit adenylyl cyclase activity. Both CUD
of Mental Disorders, 5 Edition (DSM-V), CUD is and CWS demonstrate moderate heritability, indicating
th
characterized by persistent cannabis use despite clinically that both genetic and environmental factors play a role in
significant impairment or distress, leading to functional their development. 9
impairment in various domains such as work, school, In Europe, cannabis was the most cited problem drug
relationships, and daily activities. Notably, it is estimated by new treatment clients, representing 45% of all first-time
3
that one in five individuals who have ever used cannabis, treatment entrants on the continent. However, the use
10
and one in three among those who have used cannabis on of treatments specifically designed for CUD is relatively
a weekly basis for an extended duration develops CUD. low. Available treatments primarily involve psychosocial
4
Among those who engage in recreational cannabis use, interventions such as cognitive-behavioral therapy,
approximately 22% develop CUD. Dependence is more motivational enhancement therapy, and contingency
5
common with earlier age of initiation and higher levels of management. Nevertheless, these therapies are expensive,
use. 6 and the rates of abstinence are only modest and tend to
2
Following the cessation of cannabis use, symptoms of decline after treatment ends. Approximately 80% of
cannabis withdrawal syndrome (CWS) would manifest individuals who undergo CWS tend to relapse due to
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3
within a specific time frame. According to the DSM-V, regular cannabis use within 1 – 6 months. At present,
CWS is characterized by the presence of at least three there are no medications that have been proven to be
of the following symptoms developing within 7 days of effective for treating CUD or cannabis withdrawal. Due
reduced cannabis use: (1) irritability, anger, or aggression; to these findings, medical CB use as a possible treatment
(2) nervousness or anxiety; (3) sleep disturbance; approach to improving endocannabinoid function has
(4) appetite or weight disturbance; (5) restlessness; gained traction.
(6) depressed mood; and (7) somatic symptoms, such as In this context, several CBs and CB preparations
headaches, sweating, nausea, vomiting, or abdominal pain. have attracted significant attention. Dronabinol (a
While there is a common belief that marijuana carries a synthetic THC), nabilone (a synthetic derivative of
lower risk of physical dependency compared to other THC), cannabidiol (CBD), nabiximols (a 1:1 THC/CBD
drugs, clinical evidence shows that regular marijuana combination), and PF-04457845 (a synthetic compound
smoking can lead to a specific withdrawal syndrome. that inhibits the endocannabinoid-degrading enzyme
7
The estimated prevalence of CWS ranges from 11.1% to fatty acid amide hydrolase (FAAH) were investigated as
94.2%. It has been reported that CWS occurs in up to one- potential treatments for CUD and CWS. 12
7
third of regular cannabis users in the general population
and 50 – 95% of individuals among heavy users based on The use of CBs is associated with potential side effects
treatment data or research studies. 6 and adverse events, and interactions with medications are
important considerations. Understanding and addressing
The physiological processes underlying CUD involve
the dysregulation of the endocannabinoid system, these risks is crucial for ensuring the safe and effective use
12
commonly observed in individuals with regular cannabis of medical CBs in clinical practice. This systematic review
use. Repeated exposure to marijuana leads to notable aims to provide a concise yet comprehensive overview of
desensitization and downregulation of cannabinoid the key findings from medical CB research, specifically
receptor type 1 (CB1) in the limbic system and neocortex, focusing on their pharmacological management of CUD,
along with reduced levels of endocannabinoids such as a major public health concern.
8
anandamide (AEA) and 2-arachidonoylglycerol. This 2. Methods
dysregulation manifests through the development of
cravings, tolerance, and withdrawal symptoms. 2.1. Eligibility criteria
Studying animals has been useful in understanding the This systematic review was performed and reported
potential mechanisms underlying and the risk factors for following the Cochrane Collaboration Handbook for
CWS occurrence, as rodents show both dependence and Systematic Review of Interventions and the Preferred
tolerance after long-term use of CBs. Repeated exposure Reporting Items for Systematic Reviews and Meta-
9
to either marijuana smoke or tetrahydrocannabinol (THC) Analysis (PRISMA) Statement guidelines. Inclusion was
injections in mice leads to similar physical withdrawal restricted to studies that met all the following eligibility
symptoms, such as paw tremors and head twitches. This criteria: (1) randomized trials; (2) enrolling patients

Volume 11 Issue 1 (2025) 5 doi: 10.36922/jctr.24.00066