Cannabis And Antidepressants Don’t Mix

Years before Mike Tyson reinvented himself as a comedic actor in “The Hangover,” he gained infamy as a boxer known as much for his “right hook,” as his often erratic behavior outside the ring. On numerous occasions he admitted taking Zoloft — an antidepressant — while having a love for cannabis. He once famously quipped: “I’m on the Zoloft to keep me from killing y’all.” While presumably joking, few people were laughing. Tyson’s admission prompted a number of physicians and “talking heads” to weigh in on Iron Mike’s state of mind, even blaming his erratic behavior on mixing pills and pot (notably, Tyson had penchant for polydrug use that also included numerous other psychoactive substances). 

Because individuals suffering from depression or anxiety are more inclined to use cannabis, it’s vitally important for medical professionals and patients to understand the potential risks of mixing antidepressants and cannabis. Remarkably, robust searches of Google Scholar and the National Institutes of Health PubMed website produced few quality results. Even the National Institute on Drug Abuse (NIDA) provide little information. 

The Division of Child and Adolescent Psychiatry at the University of Connecticut Health Center published a comprehensive review of scientific literature — Psychotropic Medications and Substances of Abuse Interactions in Youth — noted: “One would presume that the combination of drugs of abuse and psychotropic medications in youth might increase the probability for the occurrence of adverse effects. They observed, however, that there were a “lack of reports on interactive adverse effects between psychotropic medications and drugs of abuse.” 

They reasoned an explanation for the lack of research could be attributed to interactions being “relatively rare” or “do not happen.” Researchers explained “newer psychotropic medications have a relatively high therapeutic index and as a class, generally are not victimized by drug interactions that result in impairment of their clearance and an increase in their plasma level.” However, another possible explanation could be lack of recognition or awareness. 

That there is notable lack of research does not mean consuming cannabis while being treated with antidepressants carries no risk. According to RxList, an online index of drugs published by WebMD, the potential interaction risk between cannabis and antidepressants is “moderate.” At moderate risk, they advise: “Be cautious with this combination. Talk with your health provider.”

Risks of Drug Interactions

Selective serotonin reuptake inhibitors (SSRIs) 

The most commonly prescribed drugs to treat depression as patients report fewer side effects compared to other types of antidepressants. Popular brands include Prozac, Paxil, Zoloft, Celexa, and Lexapro.

Potential interaction risk: Moderate

Adverse interactions between cannabis seem to be rare. However, there has been some speculation fueled by isolated case reports that combining cannabis and SSRIs could increase the risk of hypomania in vulnerable populations (e.g. persons with bipolar disorder). Generally, however, many physicians favor SSRIs, because the occurrence of adverse interactions with other drugs is relatively rare.  

Serotonin and norepinephrine reuptake inhibitors (SNRIs).

Examples include duloxetine (Cymbalta) and venlafaxine (Effexor XR). 

Potential interaction risk: Moderate

A newer class of antidepressants, few adverse interactions between SNRIs and cannabis or other drugs is rare.

Norepinephrine and dopamine reuptake inhibitors (NDRIs)

Examples include bupropion (Wellbutrin, Aplenzin, Forfivo XL). Notably, NDRIs are one of the few antidepressants largely absent of sexual side effects. They’re also sometimes prescribed for ADHD and smoking cessation.

Potential interaction risk: Moderate

There have been very few adverse interactions reported.

Monoamine oxidase inhibitors (MAOIs)

Examples include tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan). MAOIs have fallen out of favor for treatment due to reported side effects and dangerous interactions (which can be fatal) with numerous foods and medications. 

Potential interaction risk: High

A search for case reports on PubMed documenting adverse interactions between cannabis and MAOIs did not produce any results. However, given the high-risk profile of MAOIs to produce significant side effects and induce adverse interactions with numerous foods and medications, suggests the use of cannabis should be avoided.

Tricyclic antidepressants

Examples include imipramine (Tofranil), amitriptyline, doxepin, trimipramine (Surmontil). While reported side effects and interactions are less common with tricyclics than MAOIs, more people report undesirables side effects with tricyclics than newer antidepressants. Consequently, they’re usually only prescribed to patients who’ve been unresponsive to other treatments.

Potential interaction risk: High

One case report documented an A 17-year-old boy with depression and insomnia prescribed 25mg of amitriptyline. After speaking with the teen’s friends and doing a search of his bedroom, parents confirmed he the only other substance he’d been using was cannabis. He was checked into ER for a racing heartbeat (tachycardia). The attending physician reported that adverse interactions could potentially be “life-threatening” and cautioned against prescribing tricyclics to treat depression or insomnia in patients who use cannabis or other drugs. Other case reports have been filed citing similar concerns.

While the risk of experiencing a significant interaction between cannabis and (most) antidepressants may be not be nearly as high as those reported with other substances — such as alcohol or nicotine — there are other potential issues that patients should consider:

Occasional use of psychoactive substances, including alcohol, has been associated with poorer responses to treatment. Makes it more difficult for physician to prescribe correct drug at the appropriate dose.“One of the most important factors when combining drugs — whether they be prescription or over-the-counter, controlled or illicit — is to be able to measure if and how much each drug is affecting mood and behavior, and what side effects each has.

Cannabis can cause users to become sleepy or drowsy, a side effect reported in other antidepressants and commonly prescribed sedative medications such as clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien). Mixing cannabis and these medications could amplify these effects.  

Increases risk of non-compliance with treatment protocols. Possibly decreases adherence to behavioral interventions. 

In patients predisposed to psychosis or schizophrenia, evidence suggests cannabis could increase risk. 

Could Cannabis Actually Work Synergistically With (Some) Antidepressants?

The psychoactive constituent in cannabis —  THC —  affects serotonin and noradrenaline, GABA and glutamate (all of which are thought to affect depression). Some preliminary evidence suggests THC in lose doses can elevate serotonin levels similar to SSRIs (notably, high doses produce the exact opposite effect.) Most importantly, studies have proven the endocannabinoid system (the body’s own cannabinoid system) plays an important role in our health and overall well-being. And, CBD — non-psychoactive — … 

These factors have led some to speculate if cannabis could potentially work synergistically with some antidepressants. It’s certainly theoretically and scientifically plausible that cannabis could interact positively to improve efficacy of other medications. However, cannabis is a highly complex plant with hundreds of different compounds and the chemical composition can vary dramatically from strain to strain. While it’s certainly possible that some strains could work synergistically with antidepressants, absent of research, at present, it’s speculative. 

produce adverse effects (or work synergistically) with antidepressants. The primary. There isn’t a significant data examining interactions between serotonergic and endocannabinoid systems, but there is emerging evidence that the two systems have a complex relationship. While theoretically possible that (some) antidepressants in (some) people could work synergistically, that’s speculative and not the purpose of this article. The purpose of this article is to objectively assess potential risks. Weed may increase the antidepressant levels in the blood and possibly increase sedation effects. It’s important to note though, significant study has not been done on modern antidepressant and marijuana interactions:

Could Cannabis Actually Work Synergistically With (Some) Antidepressants?

The psychoactive constituent in cannabis —  THC —  affects serotonin and noradrenaline, GABA and glutamate (all of which are thought to affect depression). Some preliminary evidence suggests THC in lose doses can elevate serotonin levels similar to SSRIs (notably, high doses produce the exact opposite effect.) Most importantly, studies have proven the endocannabinoid system (the body’s own cannabinoid system) plays an important role in our health and overall well-being. And, CBD — non-psychoactive — … 

These factors have led some to speculate if cannabis could potentially work synergistically with some antidepressants. It’s certainly theoretically and scientifically plausible that cannabis could interact positively to improve efficacy of other medications. However, cannabis is a highly complex plant with hundreds of different compounds and the chemical composition can vary dramatically from strain to strain. While it’s certainly possible that some strains could work synergistically with antidepressants, absent of research, at present, it’s speculative. 

Patients with anxiety or depression can use cannabis rates between two and eights times greater than general population. 

, claiming mixing cannabis and antidepressants could be a dangerous combo that could lead to a number of unwanted side effects. 

  • Antidepressant features have been ascribed to cannabis for years. The leading reason long-term cannabis users report as the basis for using are relaxation, attenuating stress, “feeling good”
  • However, there is very little research validating potential antidepressant features of cannabis. One lab study low doses of THC mimics the effects of some antidepressants by elevating serotonin. High doses of THC produce the opposite effect.
  • Evidence from human studies suggests CBD, the most prominent non-psychoactive constituent in cannabis, can alleviate anxiety and may relieve depressive symptoms.

Some evidence that isolated THC can 

Alcohol can produce severe 

Drug interactions are of significant concern

Greatest risk appears to be with tricyclics 

Given that there has been a voluminous amount of research exploring the link between substance use (and misuse) and psychiatric disorders (including anxiety and depression),  surprisingly — nay, shockingly — there are few published high-quality peer-reviewed studies investigating potential interaction between antidepressants and cannabis.

Low quality evidence doesn’t necessarily mean the data is bad. It could mean there was a high risk of bias, or it could be the design of the study: because of design limitations (e.g. reliance on self-reporting by subjects), an observational study can’t produce as high of quality evidence as a randomized controlled trial (RCT).                                         

Selective reporting

But, what does the science say? The link between depression and cannabis has been studied extensively, with research emerging that suggests: low doses of THC can improve mood, while high doses can exacerbate anxiety; CBD, the most prominent non-psychoactive constituent in cannabis appears to lower anxiety, elevate mood, and counteract potential adverse effects of THC; and, finally, while cannabis consumption does not induce depression (and can be helpful), individuals suffering from depression or anxiety are at a much higher risk (two to eight times) to misuse cannabis or develop a cannabis use-disorder.     

Cannabis works with some drugs — like opioids — as a potentiator. This can be a good thing or bad thing. If using medicinally, it can be good because people need to consume less opioids to achieve pain relief. However, it can be a bad thing if people are using recreationally and their goal is to amplify their “high.” 

Interaction Rating: Moderate Taking marijuana with fluoxetine (Prozac) might cause you to feel irritated, nervous, jittery, and excited. Doctors call this hypomania.

Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider. 

THC affects anandamide. Anandamide — the bliss molecule — reacts to THC causing a soothing sensation. Evidence similarly suggests cannabis stimulates neurogenesis in the hippocampus which could help depression. CBD, however, produces the most relieving effects and seems to alleviate anxiety. High dose THC, low CBD. CBD has not been associated with the adverse effects typically associated with THC, and appears to counteract many of these adverse effects. Hence why people should look for strains rich in CBD and not too high in THC. 

Given the link between cannabis and depression, and that many people with depression may self-medicate with cannabis, that there has been so little research on potential drug interactions between cannabis and antidepressants is — well — depressing! Most studies have relied on low quality evidence, biased samples, with a disproportionate focus on cannabis abuse and dependence — rather, than drug interactions. Given how often experts have weighed in suggesting adverse interactions, 

Nonetheless, drug interactions are commonplace. We know that alcohol and nicotine don’t interact well with antidepressants and should be avoided.

Tricylics and MAOI antidepressants have fallen out favor as they may produce….

Tricyclics — These drugs have fallen out of favor, as they seem more likely to induce adverse reactions many different substances. Some patients have reported accelerated heartbeat, hypertension, and drowsiness. Tricyclic antidepressants and marijuana can be a dangerous combination as both drugs can cause tachycardia – an increased heart rate. Tachycardia can be very serious, possibly fatal, and require emergency, medical attention. Tachycardia has been seen even in those who use marijuana regularly. 

Tricyclic antidepressants and marijuana have caused:

  • Extreme restlessness 
  • Confusion
  • Mood swings 
  • Hallucinations 
  • Chest and throat pain 

MAOI antidepressants and weed may also have adverse interactions. It appears marijuana affects how MAOIs work in the body but the full effect is not known. Modern Antidepressants and Marijuana Weed and modern antidepressants such as SSRIs and SNRIs are thought to interact less frequently and less severely than in TCA or MAOI antidepressants. 

SSRIs — Drugs like Prozac and Zoloft are commonly prescribed antidepressants. Interestingly, there’s evidence suggesting cannabis and SSRIs can produce similar emotional and physiological effects. One lab study found that low doses of THC elevated serotonin levels, while high doses had the exact opposite effect. 

The risk of mixing cannabis and SSRIs is thought to lower than Tricyclics, however, there have been a few reported cases suggesting cannabis may have been a contributing factor in triggering mania with psychosis. 

Significant adverse interactions seem rare, however, what is not well understood is to what degree cannabis use can affect outcomes. It’s definitely plausible that while cannabis may not trigger significant adverse effects with antidepressants, the risk is that other medications and protocols may not be as effective. 

Harm Reduction

Most psychiatrists (and physicians) would prefer patients completely abstained from all alcohol or any other psychoactive substance during treatment. Many patients recognize this, and concerned about being judgement unfairly, may be apprehensive to be forthcoming with their practitioner about cannabis. However, there are many practitioners are more realistic and open minded. Ideally, if you — or someone close to you — is struggling with depression and uses cannabis, it’s important to work with a professional you feel comfortable with and can maintain an honest, open communication. 

One study investigated how the occasional use of cannabis influenced the outcomes from treated anxiety and depression examining Collaborative Care for Anxiety and Panic (CCAP), a protocol that combines cognitive-behavioral (CBT) and drug treatment. There was a significant interaction between treatment groups and frequency of cannabis use for depressive symptoms (but not so for social phobia or panic disorder). In the CCAP treatment, 

Depressive symptoms in monthly users improved the same as those who used less than monthly. However, monthly users undergoing typical care experienced significantly more depressive symptoms than those who used less frequently, thereby leading the researchers to suggest that for occasional cannabis users, a combined CBT and medication treatment “may be a promising approach for the treatment of of depression” among this population. 

Future research:

We know that CBD not only possesses antipsychotic and antianxiety effects, but can reduce the adverse effects associated with THC — most notably, anxiety. Further, CBD doesn’t seem to produce any notable side effects, even in high doses. Given its potential to relieve anxiety, tension, and depression, further research should focus on how CBD interacts with antidepressants. To date, no credible studies have investigated how CBD interacts with other antidepressant medications — adversely or synergistically. 

Moreover,  many long term cannabis users report using cannabis becuase it helps them relax, cope with stress, and reduce depression and anxiety. More studies should be done to investigate potential adverse conseunces. 

The risk of adverse interactions differs from drug to drug.  

Many studies rely on low quality evidence, use bias samples, while focusing on cannabis abuse and dependence. After controlling for cofounding variables, while cannabis doesn’t appear to cause depression, those with depression or anxiety are more likely to misuse cannabis. 

If someone is being treated for depression, ideally they would abstain from any other substances including nicotine and alcohol as

One study showed boacco use was associated with more negative effects than cannabis.  A high quality study found CBD reduced anxiety, cogntive impairment and discomfort. 

the relationship between cannabis use and depression or anxiety remains controversial. Studies have confirmed there is a link between cannabis use and depression. However, later studies have found that while individuals with depression and anxiety may use cannabis more than others, cannabis doesn’t cause depression. In high doses,  particularly among infrequet users, high levels of THC can induce anxiety, and even episodes that resemble a panic attack along with intense fear and anxiety.  Long=term users report cannabis helps relieve tension and helps them relax, and cite these reasons as being a primary factor influencing their decisiion to use. 

those with anxiety and depression are more likely to use cannabis, but it’s unlikely that cannabis use causes these symptoms. “[I]f cannabis use were to have been responsible for the precipitation of anxiety disorders, one would have expected an increase in the number of people presenting with these disorders in recent years, as the prevalance and extent of cannabis use has increased in recent times.”

 Seems to be paradoxical that people use cannabis to alleviate symptoms, while these symptoms are a commonly reported adverse effect. How can that be? The effects seem to be dose dependent. Low doses can have antidressive effects, whereas higher doses produce just the opposite. Cannabis consumption and depression co-occur at high rates.  – At high doses, anxiety is the most commonly reported adverse effect. More common in occasional users.  – Evidence does not suggest cannabis use alone causes depression or anxiety related disorders, but could be a risk factor along with other factors.  – Chronnic use is associated with higher rates of depression, and depression is associated with higher rates of cannais use. 

Scientists have long studied the link between cannabis and depression. There is some evidence to suggest that cannabis — in low to moderate doses — has the potential to alleviate depression. A preclinical study conducted by Canadian researchers found low doses of THC can produce similar effects to 

CBD (the most prominent non-psychoactive constituent in cannabis)

been studying the link between cannabis consumption and depression for sometime. After controlling for confounding factors, an increasing body of research has found that while cannabis does not cause depression. In fact, early studies have found that CBD — the most prominent non-psychoactive constituent in cannabis — may alleviate anxiety and depression, and appears to produce antipsychotic effects. Moreover, low doses of THC appears to produce similar effects to SSRIs. (High levels do just the opposite.) 

However, there are other some notable risks. How does cannabis interact with antidepressants. It’s widely accepted that those being treated for depression should not use alcohol. Similarly, evidence suggests cannabis may interact adversely with antidepressant medication. 

There may by a negative link between some types of antidepressants and marijuana. Antidepressants are generally used to treat depressive disorders and research shows that people with depression tend to use illicit drugs more than the average population. Of those who do use drugs, it’s likely many with depression also use marijuana. The key, however, is that most people don’t report this use to their doctor, so there is less information on antidepressants and marijuana than for other drug interactions. 

There are some case reports though involving weed and antidepressants that show some types of antidepressants are negatively affected by marijuana – sometimes dramatically so. 

Types of antidepressants include: 

Tricyclic antidepressants (TCAs) 

Monoamine oxidase inhibitors (MAOIs) 

Selective serotonin reuptake inhibitors (SSRIs) 

Other (various) 

It’s also important to note chronic use of more than small amounts of marijuana acts as a depressant and this depressant effect can reduce the efficacy of antidepressants. 

TCA and MAOI Antidepressants and Marijuana 

Antidepressants and marijuana can be dangerous depending on the type of antidepressant. 

Learn about the risks of weed and antidepressants. 

are  Cannabinoid receptors suggests are prominent in ocular tissues responsible for regulating intraocular pressure, and are  Cannabinoids are also neuroprotective

Through extensive lab research, cannabinoid receptors — particularly CB1 — and other undiscovered pathways, have demonstrated robust expression in ocular tissues associated with regulating intraocular pressure and layers of the receptors. In other words, cannabinoids have the potential to reduce eye pressure and provide a neuroprotective effect on retinal cells.