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Why cannabis use makes some people feel "high" and others paranoid

A new study led by the Medical University of South Carolina (MUSC) has explored the impact of individual variations in THC metabolism on the risk of cannabis use disorder (CUD) among young adults

The research reveals that genetic differences in the metabolic breakdown of THC, the principal intoxicating component of cannabis, could significantly affect an individual’s response to the drug and their susceptibility to CUD.

What is cannabis use disorder?

Cannabis use disorder affects about one in five cannabis users, leading to withdrawal symptoms, a heightened need for the drug to achieve similar effects, and challenges in reducing use. 

The researchers discovered that genetic variations influencing the efficiency of THC metabolism could intensify cannabis’s effects, as approximately a quarter of the population possesses a gene variant that reduces their capacity to metabolize THC efficiently.

Focus of the study 

The scientists focused on young adults aged 18-25, who are at a higher risk for cannabis use disorder, to explore how these metabolic differences correlate with the users’ reported experiences. 

Blood samples and questionnaires were utilized to distinguish between participants as either normal or slow metabolizers of THC, and to assess the subjective effects they reported from cannabis use.

How people metabolize cannabis

“Unfortunately, we’re just beginning to understand some of the effects of how people metabolize and process cannabis,” said lead author Christal Davis, an expert in psychiatric genetics and substance use at the University of Pennsylvania and former psychology intern at MUSC.

The researchers recruited 38 young adults aged 18-25 with CUD and 16 with a non-CUD substance use disorder. This age group was chosen since they are three times more likely to have cannabis use disorder than teenagers or adults over 26.

“This age group is super important to study because the brain is still developing up through young adulthood,” said senior author Rachel Tomko, a clinical psychologist at MUSC. “So, this is a key time for intervention.”

Sex-specific differences in THC metabolism

A surprising finding was the sex-specific differences in THC metabolism’s impact. For young females with cannabis use disorder, being a slow metabolizer was more common compared to those with non-CUD substance use disorders, suggesting a greater risk for developing CUD among this group. 

Conversely, young adult males with the slow-metabolizing gene variant reported experiencing more adverse effects during their initial cannabis use.

Despite these negative effects, the presence of concurrent positive experiences may drive slow metabolizers to continue using cannabis.

“We might think that if you’re experiencing negative effects, you don’t continue to use, but in the face of positive, rewarding effects, maybe you do,” Tomko said.

Potential risk factors for cannabis use disorder

These findings highlight the importance of educating teens about the varied effects of cannabis, including the potential risk factors for cannabis use disorder.

Programs like the Just Say Know Prevention Program  at MUSC aim to increase adolescents’ understanding of drug addiction neuroscience.

As cannabis products grow in potency and societal acceptance, further research is crucial for identifying CUD risk factors and informing treatment strategies for vulnerable groups like adolescents. 

This study, published in the journal Addictive Behaviors, opens the door to exploring treatment options that may adjust THC metabolism as a means of combating CUD, highlighting the complex interplay between genetics, substance use, and addiction.

More about cannabis use disorder 

Cannabis use disorder (CUD) arises when an individual’s use of cannabis leads to clinically significant impairment or distress.

This condition has been increasingly recognized and studied due to the widespread use of cannabis globally and changes in its legal status in many areas.

While many people use cannabis without significant issues, for some, it can lead to problems that affect their daily lives, relationships, and health.

Cannabis use disorder and mental health 

One of the primary concerns with CUD is its impact on mental health. Research has shown that regular and heavy use of cannabis can increase the risk of developing psychiatric disorders such as depression, anxiety, and in some cases, psychosis, especially in those with a predisposition to these conditions. 

There’s also a well-documented association between cannabis use and schizophrenia, where cannabis can precipitate the onset of schizophrenia in vulnerable individuals or exacerbate existing symptoms.

Cognitive function is another area affected by CUD. Users may experience impairments in attention, memory, and decision-making abilities.

These cognitive effects can have significant implications for academic performance, employment, and the capacity to perform daily tasks.

Physical health risks

Physical health risks are also associated with CUD. Smoking cannabis can lead to respiratory problems similar to those caused by smoking tobacco, including chronic bronchitis and lung infections.

Additionally, cannabis use has been linked to an increased risk of testicular cancer and may impact heart rate and blood pressure, which could be problematic for individuals with heart conditions.

Behavior issues from cannabis use disorder

Social and behavioral issues are notable in individuals with CUD. The disorder can lead to increased absenteeism from work or school, lower overall life satisfaction, and difficulties in maintaining healthy relationships.

It can also result in legal and financial problems due to the costs associated with purchasing cannabis and potential legal issues related to its use.

Cannabis dependency 

Importantly, CUD can lead to dependency, where individuals find it difficult to reduce consumption despite wanting to do so and may continue to use cannabis despite experiencing negative consequences.

Withdrawal symptoms, such as irritability, mood and sleep difficulties, decreased appetite, restlessness, and various forms of physical discomfort, can make cessation challenging.

Potential benefits of cannabis

As mentioned previously, cannabis does show potential benefits in many circumstances. Researchers have found that cannabis may provide therapeutic benefits for a range of health issues.

Studies suggest that compounds in cannabis, particularly CBD and THC, interact with the body’s endocannabinoid system. This system plays a role in regulating pain, inflammation, mood, appetite, and other physiological processes.

Pain relief

Cannabis has shown potential as an alternative treatment for chronic pain. THC and CBD may help reduce pain and inflammation associated with conditions like arthritis, fibromyalgia, and nerve pain. Some patients report that cannabis enables them to reduce their use of prescription painkillers.

Alleviating symptoms of neurological disorders

Certain neurological disorders like multiple sclerosis, Parkinson’s disease, and epilepsy may respond favorably to cannabis.

CBD has demonstrated anticonvulsant properties that can help control seizures. Cannabis may also alleviate muscle spasms, tremors, and pain related to these conditions.

Mental health benefits

Some evidence indicates that cannabis could have benefits for mental health. CBD has shown promise for reducing anxiety and may have antidepressant effects.

Cannabis may also help improve sleep for those with insomnia or PTSD-related sleep disturbances. However, more research is needed on the psychiatric effects of long-term cannabis use.

While studies have revealed potential medical benefits, it’s important to note that cannabis affects each individual differently. Dosage and cannabinoid ratios can influence the effects.

Consulting with a healthcare provider is advised to determine if medical cannabis is appropriate for a specific condition. As with any treatment, cannabis carries possible risks and side effects that should be carefully considered.

In summary, while cannabis is often viewed as a relatively harmless substance, especially compared to other drugs, the development of cannabis use disorder can have wide-ranging and serious impacts. It can damage an individual’s mental and physical health, cognitive function, and overall quality of life. Recognizing the signs and seeking appropriate treatment is essential for those affected.


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