مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Neuroprotective Potential and Psychiatric Risks of Cannabis: A Differential Risk-Benefit Analysis of THC and CBD in Neurological Versus Psychiatric Disorders
Neuroprotective Potential and Psychiatric Risks of Cannabis: A Differential Risk-Benefit Analysis of THC and CBD in Neurological Versus Psychiatric Disorders
Introduction: Cannabis has gone an astonishing path - from an ancient traditional herbal remedy to an object of significant controversy as a drug. In the modern world, it is the point of convergence for hopes and fears: it can relieve seizures, reduce spasticity, and treat severe neurological pain, and at the same time carry threats of psychiatric harm, memory deficits, and addiction. That same plant capable of calming the overactive nervous system of a child with drug-resistant epilepsy can, under different conditions, induce a psychotic relapse or damage memory in an adult. Modern cannabis contains THC concentrations 5-7 times higher than it did a hundred years ago, and not only do we lack sufficient long-term safety data in that area, but most of the existing cannabis research is underdeveloped: 74% of studies include fewer than 40 subjects, and the vast majority are short-term studies (<=8 weeks). Distinguishing cannabis’s therapeutic benefits alongside its harms is not an abstract issue, but an essential act for public health.
Methods: Evidence was gathered from peer-reviewed papers in the last 5 years, using randomized controlled trials, large observational cohorts, and mechanistic studies. In the current analysis, human subjects were included when dosing regimens and cannabinoid content were precisely specified, valid outcome variables were used, and subjects were followed for at least four weeks unless the primary purpose was mechanistic. Trials with unstandardized outcomes, ambiguous formulations, or those designed solely on the basis of anecdotal support were not taken into consideration for examination.
Results: Cannabis shows its strongest benefits in neurological diseases. In multiple sclerosis (MS), studies reported significant improvements in muscle spasticity and inflammatory activity, with mean improvements of 1.3 points on the Modified Ashworth Scale (p<0.01). In childhood drug-resistant epilepsy, CBD-rich extracts elicited >=50% seizure reduction in 43-52% of subjects, compared with 22-27% receiving placebo (relative risk ~2.0). Preliminary evidence for early Parkinson's disease suggests potential motor and sleep benefits, but study sample sizes are still small (<30).
On the contrary, in psychiatric disorders - like anxiety, depression, insomnia, ADHD, PTSD, and OCD - minimal benefit was observed, and studies could not establish statistically significant differences in improvements over placebo despite repeated subjective improvements reported. Gilman et al. (2022) also reported that 17.1% of participants who were allowed immediate medical marijuana card use developed cannabis use disorder within the first 12 weeks, with no measurable difference for pain, anxiety, or depression scores.
Those who were vulnerable or had a psychiatric disorder were especially at risk. Cannabis use was associated with a sixfold (6x) greater risk of discontinuing antipsychotics, a 2-3x increased risk of psychosis relapse, and increased suicide attempt rates (odds ratios ~1.5-2.0). Perinatal exposure carried increased risks as follows: 40% for NICU admission, 17% for low birth weight, 10-15% for premature birth, and 70% for being at fault in a car accident.
Mechanistic investigations reveal that the anti-anxiety and anti-seizure actions of cannabinoids are rooted in the activation of serotonin 1A receptors and the modulation of the TRPV1 pain pathways, while THC's euphoric and anxiety/psychosis-inducing actions arise through CB1 receptor agonism (binding). High-THC varieties exaggerate psychiatric risk, but THC/CBD-balanced derivatives might reduce some of the side effects. Notably, THC derivatives like K2 carry a significant risk of acute psychosis and violent outcomes, making them dangerous in illegal use.
Tolerance and dependence profiles are comparable to benzodiazepines: relief at first, followed by tolerance at higher dosages, and withdrawal symptoms upon cessation, although without GABAergic physiological dependence.
Conclusion: Cannabis provides clear, evidence-based and mechanistically studied benefits in very specific severe neurological illnesses like MS, refractory epilepsy, and chronic neuropathic pain. In psychiatric conditions, however, the lack of objective improvement, coupled with higher risks of dependence, psychiatric relapse, and cognitive decline, makes it unsuitable as a primary treatment. Further clinical use should be targeted and use CBD-rich or balanced over high-THC extracts. Use should be avoided in people under the age of 25 (before the standard age of frontal lobe full development) or with psychiatric risks, and frequency should be restricted to minimize tolerance and dependence. Considering that cannabis use is a growing issue in our society, large, longitudinal studies with standardized dosage and prolonged follow-up are urgently needed for the refinement of guidelines and protection of public health.