Medicinal Use of Cannabis: Drug Interactions

By Sechat Editorial Team

Among the various cannabinoids present in the cannabis plant, some such as cannabidiol (CBD) and tetrahydrocannabinol (THC) stand out for their health benefits and treatment possibilities. Whether helping people with cancer, reducing inflammation, or decreasing epileptic seizures in patients with neurological disorders, the therapeutic potential of this plant offers many a chance at a better life.

However, despite its benefits, patients should proceed with caution as the compounds in the plant can interact with other compounds. Although more conclusive studies are needed before the full extent of drug interactions of cannabis derivatives can be determined, researchers have already identified some of them.

THC

The most significant drug interactions involving cannabis are those related to the P450 enzyme family (CYP), which are responsible for metabolizing most medications. When inhaled, THC accelerates the activity of the CYP enzyme, resulting in accelerated drug breakdown. This breakdown leads to lower overall levels of the substance in the body.

Medications susceptible to these interactions include: clozapine, duloxetine, naproxen, cyclobenzaprine, olanzapine, haloperidol, and chlorpromazine.

CBD

Another cannabis compound that also interacts with CYP, inhibiting enzymes responsible for drug degradation, is CBD. The concurrent use of this substance with selected medications may result in intensified levels of the phytocannabinoid in the body.

Potential medications include: Selective Serotonin Reuptake Inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, beta-blockers, and opioids (including codeine and oxycodone). CBD can also increase concentrations of: macrolides, calcium channel blockers, benzodiazepines, cyclosporine, sildenafil, antihistamines, haloperidol, antiretrovirals, and some statins.

Some medications may inhibit the enzyme that metabolizes CBD, resulting in the accumulation of cannabidiol in the body. Some of these include ketoconazole, itraconazole, ritonavir, and clarithromycin. Other drugs act in the opposite way, speeding up CBD metabolism by the enzyme and resulting in reduced compound bioavailability. Some of these drugs include phenobarbital, rifampicin, carbamazepine, and phenytoin.

CBD drug interactions can vary depending on whether the drug increases or decreases CYP enzyme activity.

Alcohol

Alcohol can exacerbate the effects of cannabis. Researchers have found that low doses of the compound – approximately 0.065% – significantly increased THC blood levels. This increase can impair cognition and judgment, as well as cause other side effects such as dizziness and drowsiness, so use caution when combining the two.

SSRIs

Not much is known about potential drug interactions with Selective Serotonin Reuptake Inhibitors (SSRIs), a class of medications commonly used as antidepressants. However, studies highlight the relationship between the medicinal use of cannabis and demonstrated benefits in controlling depression. 

The U.S. Department of Health issued a special warning in a presentation on interactions with Prozac, stating: "Using marijuana with fluoxetine (Prozac) can make you feel irritable, nervous, agitated, and excited. Doctors call this hypomania."

As so little information is currently available, patients on SSRIs should consult a doctor before using cannabis.

Tricyclic Antidepressants

Another class of medications to watch out for are tricyclic antidepressants (TCAs). The UK National Health Service noted that "Medicinal cannabis or marijuana may interact with tricyclic antidepressants, such as amitriptyline, imipramine, and dothiepin." The rationale behind this is that the combination of the two may result in high blood pressure (hypertension) or rapid heart rate (tachycardia). Other potential side effects may include mood changes, restlessness, confusion, and hallucinations," the document highlighted.

Opioids

One of the most promising aspects of medicinal cannabis is its therapeutic potential in treating opioid dependence. Studies reveal that patients who have access to medicinal marijuana reduce opioid use by 40% to 60%.

Interestingly, vaporized marijuana has been shown to enhance the analgesic aspects of opioids without affecting their plasma levels.

CNS Depressants

CNS depressants are a class of drugs that reduce stimulation by lowering neurotransmission levels in the Central Nervous System. The result is decreased brain activity that promotes muscle relaxation and a sense of calm. These medications include clonazepam (Klonopin), lorazepam (Ativan), and zolpidem (Ambien), among others.

The U.S. Department of Health noted that cannabis enhances the CNS depressant effects when combined with alcohol, barbiturates (anticonvulsants), and benzodiazepines. The use of medicinal marijuana can amplify the drowsy effect of these medications.

Calcium Channel Blockers

The use of cannabis can affect certain calcium channel blocker medications, such as Diltiazem, a channel blocker and antihypertensive. Diltiazem manufacturers state that caution should be exercised when combining the two, as Diltiazem may enhance the effects of THC.

Blood Thinners

Patients using anticoagulants like Warfarin (also known as Coumadin) should avoid cannabis use. The U.S. Department of Health warns that "smoking marijuana" while taking Warfarin (Coumadin) can increase the chances of bruising and bleeding."

Theophylline

Theophylline is a bronchodilator (a medication that helps increase airflow to the lungs). A 2014 study observed that cannabis can decrease theophylline levels when smoked.

SSRIs, Tricyclic Antidepressants (TCAs), and Benzodiazepines

CBD is a potent inhibitor of CYP2D6. Since this enzyme is responsible for metabolizing different types of antidepressants, CBD can increase serum concentrations of SSRIs, tricyclic antidepressants, and benzodiazepines.

Anticonvulsants

CBD is often used to help treat seizures and epileptic patients. However, it can alter the levels of other anticonvulsants if taken concomitantly. The use of CBD in conjunction with Clobazam, a sedative used to treat seizures, results in higher levels of Clobazam in children with epilepsy due to potent inhibition of the CYP2C19 enzyme.

Researchers also noted that abnormal liver function test results were found in participants who took the anticonvulsant Valproate together with CBD. Therefore, extreme caution should be exercised when combining CBD with anticonvulsants or other epileptic drugs. Researchers recommend mandatory monitoring of drug levels to observe patients' liver functions.

Conclusion

Cannabis has a wide range of therapeutic benefits. However, its concurrent use with other drugs can result in a variety of drug interactions. Given that THC and CBD affect the body uniquely, patients should exercise great care when combining marijuana with other medications. Consult a doctor before starting the use of medicinal marijuana. In most cases, no change or alteration in medication dosage is guaranteed.

In terms of safety, groups that are especially vulnerable to the effects of cannabis include elderly patients, individuals with autoimmune or liver diseases, and patients prone to psychosis (especially teenagers). It is advisable to consult a doctor if you have any questions about how marijuana may affect you.