Dangers of Recreational/Medical Cannabis Use

Dangers of Recreational/Medical Cannabis Use

According to the United Nations Office on Drugs and Crime, cannabis is the most widely used illicit drug in the world. While cannabis is increasingly being used as a recreational drug in addition to its medicinal use to treat chronic pain, there is little evidence of its safety.

Some data suggest that neurocognitive functions are impaired by cannabis use, with anatomical deteriorations supporting these observations. The risks increase with the earlier age of onset.

As with any other medication, these risks should be weighed alongside the benefits before making a decision about cannabis use.”

Learn: Side effects of recreational and medical cannabis.Photo credit: OMfotovideocontent / Shutterstock.com

introduction

Cannabis sativa is the source of cannabis and its derivatives. Known by several names, such as marijuana for dried flower buds and hashish for plant resin blocks, cannabis contains several bioactive compounds such as flavonoids, cannabinol and cannabinoids.

The most notable cannabinoids found in cannabis include the powerful psychoactive compound delta-9-tetrahydrocannabinol (THC) and the anti-inflammatory cannabidiol (CBD). Both active ingredients act on the cannabinoid receptor 1 (CB1), with THC being a partial agonist and CBD being a negative allosteric modulator.

CB1 receptors are most concentrated in the central nervous system (CNS). These receptors are neurochemically similar to opioid receptors and thus influence the nociceptive pathways in the brain.

Receptor binding by cannabinoids results in stimulation of the endogenous cannabinoid system, altering the levels of endogenous cannabinoids (eCBs), with a concomitant reduction in the release of gamma-aminobutyric acid (GABA) and glutamate. The eCBs are involved in reward, memory, learning and pain pathways.

In addition, CB1 and CB2 receptors can increase the release of dopamine while reducing the release of acetylcholine and norepinephrine.

Now that many American states have legalized cannabis, the already high rate of cannabis use is increasing starting from the age of 16. Additionally, medical cannabis use is becoming more common, with 40% of cancer patients using cannabis for pain management when it is legally available, such as in Canada, Germany and Israel.

Cannabis-based medicines (CBMs) such as dronabinol and nabiximols are also made available. These are used in capsule form (Dronabinol) or as an oral spray (Nabiximols), as well as oral or inhaled solutions of generic THC. Medical cannabis is also used instead of standard therapy for conditions such as refractory epilepsy, schizophrenia or multiple sclerosis.

All of this takes place in the context of limited evidence that cannabis is safe. Additionally, studies are limited by reliance on a single federal cannabis source, recall bias, small sample sizes, and poor external validity.

What did the study show?

A previous Cochrane review in 2017 reported that most studies were of low to moderate quality. The use of medical cannabis could increase the proportion of people who were able to reduce their pain to half of existing levels or less.

However, the overall impression of a change in pain treatment among patients was very low, as the negative effects of cannabis use led to multiple terminations of medical cannabis studies.

Although the frequency of serious adverse events was not increased with medical cannabis compared to placebo, the former appeared to affect the nervous system, with a higher risk of psychiatric disorders. Long-term risks were poorly assessed. In addition, some authors have concluded that the cost-benefit ratio of medical cannabis is unfavorable.

Cannabis for pain relief

For cancer patients with chronic pain, who represent 70% of patients with advanced malignancy, opioids are a first-line treatment recommended by the World Health Organization (WHO). While high-quality studies comparing opioids and THC are lacking, it appears that nabiximols provide better pain relief than placebo at low to moderate doses with adequate tolerability.

High doses of THC cause sedation, while the THC/CBD combination provides superior analgesia compared to THC or placebo. In fact, this combination has been maintained for up to two years without the need for increased opioid medication, while in some cases patients' opioid dosages have been reduced by 50%.

Adverse CNS and intestinal effects occurred more frequently with oromucous nabiximols and THC. Therefore, there is an urgent need for further research to determine the optimal dosage and route of administration.

Cognitive effects

Cannabis users tend to show deficits in executive function, with poorer memory and attention than non-users. This appears to be dose dependent and affects cognition, reward and motivation.

Young adults with cannabis use disorder (CUD) may have cognitive impairments due to disturbances in the emotional domain. This reduces normal cognitive control and decision-making ability in emotionally stressful situations.

Studies of brain electrical activity suggest that cannabis users exhibit increased cortical activation at rest, perhaps because the normal inhibition of unnecessary processes that generate background noise and reduce brain efficiency is impaired by cannabis.

Acute cannabis use impairs working, verbal and visual memory, as well as episodic memory and attention with higher impulsivity. In fact, small changes can be detected within a week of heavy cannabis use.

Memory and learning tests consistently produce poorer results in cannabis users. However, these cognitive tests must take family background and other individual factors into account.

Chronic cannabis use tends to impair memory, in addition to significant brain dysfunction affecting visual-motor pathways. When chronic smokers who were abstinent for an average of 15 hours were compared with chronic tobacco users, the former showed poorer learning and memory abilities, with more disorders and greater forgetfulness. Reaction times were also longer in chronic cannabis users, particularly when sustained attention was required.

Interestingly, cannabis use on three or fewer days per week was found to improve overall health compared to heavy use, with better appetite and depression comparable to those who quit cannabis altogether. Despite this, improved cognition was only associated with previous cannabis users.

Similar memory reversion was found with the use of an adenosine A2A receptor (A2AR) antagonist in chronic users, perhaps because it increased synaptic plasticity in the hippocampus from its depressive state.

Structural effects

Neuroimaging has shown the occurrence of abnormalities in hippocampal gray matter volume and density in cannabis users. White matter is also involved as it is a dense site for CB1 receptors.

The association of poor working memory, a brain function that primarily develops during adolescence, is more common among frequent adolescent cannabis users compared to adults. This is reflected in impaired activation of posterior parietal cortical areas and increased activation of other parts of the prefrontal cortex.

The former may indicate a risk factor for cannabis use, as it showed no difference between cases of single and repeated use. Conversely, cannabis users exhibit neurological changes that indicate an adaptation process in which they use relatively inefficient strategies to achieve comparable results to non-users.

Cannabis may reduce the aesthetic pleasure of listening to music through reward pathways in the brain. This was compensated for by adding CBD to the drug.

Cannabis use before the onset of schizophrenia is associated with neural gray cell atrophy, but not in patients with schizophrenia or bipolar disorder who took the drug after their diagnosis. There is evidence that adolescent cannabis use may prevent or ameliorate neuronal impairment in psychotic patients; However, this needs to be further investigated.

Is cannabis carcinogenic?

Patients with throat cancer are more likely to use cannabis, but not patients with other head and neck cancers. These patients were also more likely to have chemoradiotherapy than surgery alone. Smoking cannabis produces toxins that can cause head and neck cancer, as well as immunosuppressants and mutagens.

A previous study showed a threefold risk of head and neck cancer with cannabis use, particularly in people under 55 years old. However, this has not been confirmed.

Biological plausibility exists because cannabis upregulates epidermal growth factor receptor (EGFR) and its downstream elements, which are found at higher levels in most head and neck squamous cell carcinomas.

Smoking cannabis also alters the oral microbiome in the throat and the side of the tongue, where most of these cancers occur.

Is cannabis addictive?

Addiction is described by various models, of which the three-stage model seems to fit CUD. These are the basal ganglia, which provide the feeling of intoxication; the amygdala, which produces negative feelings during withdrawal; and the prefrontal cortex, which is responsible for preoccupation with or anticipation of the next dose. Cerebellar CB receptors may also be involved.

Approximately 10% of cannabis users experience CUD, with over half of these being due to genetic effects. Importantly, the prevalence of CUD is increasing over time, with more young people between the ages of 12 and 17 beginning cannabis use than young adults under the age of 25. Therefore, it is important to recognize risk factors for this disease.

Chronic cannabis use can permanently alter cognition by altering brain processing in pathways such as the prefrontal-limbic system network. Abstinence for more than a month was not associated with improved response to emotional stimuli in chronically addicted users.

These results suggest that chronic cannabis use may lead to addictive changes that cause persistent changes in emotional processing.”

This effect appears to be characterized by a shift from reduced coupling of the medial orbitofrontal cortex (mOFC) with the dorsal striatum to improved coupling, which may reflect the onset of addiction. Furthermore, this switch from ventral to dorsal striatal coupling with the prefrontal cortex could explain how voluntary drug ingestion transitions into habitual ingestion or dependence through impaired impulse inhibition.

Conclusions

The current review requires much larger studies with rigorous quality standards to produce results with external validity. This research is urgently needed as recreational and medical cannabis becomes legalized in many societies, particularly in the United States, where dozens of states have taken such measures.

Therefore, it has become imperative to advance current understanding of both the basic science and clinical applications of cannabis.”

Reference:

• Urits, I., Charipova, K., Gress, K., et al. (2021). Nebenwirkungen von Freizeit- und medizinischem Cannabis. Bulletin für Psychopharmakologie. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063125/.

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