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How Cannabis Interacts With Antidepressants

Cannabis and antidepressants both work to boost happy brain chemicals, and even give rise to the creation of new brain cells. However, using the two together can result in potentially dangerous interactions. Some antidepressants don’t mix with cannabis, whereas others are much more compatible. Find out about these interactions in detail below.

The relationship between cannabis, mental health, and antidepressants.

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Cannabis and mental health share a controversial—and at times paradoxical—relationship. Some cannabis smokers use the herb to elevate their spirits and boost their mood, and some even need the plant to help them get out of bed in the morning. In others, cannabis can invoke feelings of paranoia and other mood disturbances.

There are conflicting views in healthcare when it comes to cannabis and depression. Some practitioners hold the belief that cannabis may help to take the edge off some symptoms, whereas others believe excess cannabis use leads to symptoms of depression and interacts dangerously with conventional medication for the condition.

Continue reading to explore the relationship between cannabis, depression, and antidepressant medication.

Cannabis and Mental Health: A Complicated Relationship

Cannabis affects different people in different ways, especially when it comes to mental health. Most people familiar with the effects of the herb will vouch that it does a reliable job of improving mood. A few tokes on a joint can boost dopamine levels, reduce feelings of nervousness, and soothe the body.

These outcomes help many people across the world deal with certain mental health conditions. However, research also associates cannabis with adverse mental health outcomes. Although no research draws a direct link between consuming cannabis and depression, surveys report a high incidence of depression in heavy cannabis smokers [1] compared to non-smokers.

Cannabis may also trigger underlying health mental conditions in some individuals. The psychotropic effects of the herb can stoke symptoms of schizophrenia and psychosis—serious mental health disorders—in those predisposed to the conditions.

The cannabinoid THC produces the psychotropic effects of cannabis; however, over 100 cannabinoids exist in the plant, and most are non-psychotropic. In fact, molecules such as CBD can help to inhibit some of the effects of THC, and show potential in the field of mental health [2] .

Cannabis and Antidepressants

Staggeringly, over 260 million people [3] across the world suffer from depression, and millions take antidepressant medication [4] to manage their symptoms. However, people with depression are more likely to smoke cannabis. Both weed and antidepressants create profound short and long-term changes in the brain, and frequently interact with each other. Before we delve into the safety issues of this combination, let’s explore the unique effects of each drug.

How Does Cannabis Affect the Body?

Cannabis interacts with several major physiological systems. As their names suggest, cannabinoids primarily target the endocannabinoid system (ECS). The ECS plays a fundamental role by regulating many other systems and helping the body maintain biological equilibrium, aka homeostasis.

The ECS features three main components: receptors, signalling molecules (endocannabinoids), and enzymes that create and break down these molecules. Interestingly, cannabinoids such as THC share a similar molecular structure with endocannabinoids, allowing them to bind to the same receptors.

After taking a hit from a joint or bong, THC diffuses through the alveoli in the lungs, enters the bloodstream, and passes into the brain. Here, the molecule binds to CB1 receptors of the endocannabinoid system, where it gives rise to its psychotropic effects—a high.

This binding also boosts dopamine levels and neuronal activity in the brain. Dopamine plays a role in the brain’s reward system and makes us feel pleasure after consuming a certain substance or acting in a certain way.

This surge in feel-good neurotransmitters might help some users feel relief from their depression symptoms, at least for a while. However, with long-term use, THC begins to blunt the dopamine system [5] and may even block the dopamine response to other stimuli that usually release the chemical.

The neurogenesis hypothesis suggests that depression may arise from an alteration in the creation of new neurons in the brain [6] . The rate of neurogenesis may underpin a healthy and happy brain. Negative events, such as stressful or traumatic experiences, may alter this rate, leading to depression. Evidence suggests that the endocannabinoid system helps to regulate neurogenesis, and cannabinoids such as THC and CBD may help drive this process [7] in the brain.

CBD also interacts with numerous bodily systems, including serotonin pathways. As a key regulator of mood and feelings of well-being, serotonin plays an important part in how we feel. The ability of CBD to interface with this system means the cannabinoid may help to take the edge off feelings of nervousness and agitation [8] .

How Do Antidepressants Affect the Body?

Antidepressants ultimately aim to improve the symptoms of depression by altering brain chemistry. Although depression has no single cause, a shift in neurochemistry following addiction, emotional life events, or genetic factors may lead to feelings of hopelessness, low mood, and low self-esteem.

Antidepressant medication helps to regulate neurological activity by interacting with systems in the brain that govern mood. Some of these chemicals seek to increase and prolong the presence of brain chemicals, such as serotonin, in the synaptic space. Research also suggests that antidepressants might improve depression symptoms by improving neurogenesis rates within the depressed brain, similar to cannabis.

Interestingly, antidepressants appear to recruit the endocannabinoid system [9] , and prolonged use may be involved in long-lasting neuroplastic changes in the brain.

Cannabis’ Interaction With Antidepressants

Because both cannabis and antidepressants may provide symptomatic relief, some users might think taking the two together will provide even better results. However, taking cannabis alongside conventional medication can produce dangerous side effects when done incorrectly. Check out the list below to find out which antidepressants interact with cannabis.

Types of Antidepressants

The following drugs may fall into the same “antidepressant” category, but they work in a variety of ways. Varying mechanisms of action mean different drugs interact with cannabis in more or less dangerous ways. Take a dive into the most common antidepressants below and find out if they are safe to take alongside the herb.

Tricyclics

Tricyclics are among the oldest antidepressants developed. Due to their early occurrence, they generally produce more side effects than newer medications. Known by the brand names Tofranil and Surmontil, tricyclics work by changing brain chemistry. These molecules block the reuptake of the neurotransmitters norepinephrine and serotonin, ultimately boosting their levels in the brain.

Potential Side Effects

Common side effects of tricyclics include drowsiness, constipation, blurred vision, and a drop in blood pressure. Unfortunately, these medications have a high likelihood of negatively interacting with cannabis. Possible side effects of combining the two include potentially life-threatening increased heart rate (tachycardia).

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors include branded drugs such as Prozac. These drugs interact with serotonin receptors in the brain, latching onto these sites in the synapses of neurons and preventing cells from reabsorbing serotonin. High levels of serotonin remain in the synaptic space, where it exerts mood-enhancing effects.

Potential Side Effects

Taken alone, SSRIs can produce side effects such as anxiety, shaking, weight loss, and dizziness. These drugs also pose a low–moderate risk of negatively interacting with cannabis.

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors work by prolonging the presence of neurotransmitters in the brain. Dopamine, serotonin, and norepinephrine all fall into the monoamine chemical class. The enzyme monoamine oxidase metabolises and breaks down these molecules. By inhibiting the action of these enzymes, MAOIs lead to enhanced levels of monoamines in the synapses.

Potential Side Effects

MAOIs negatively interact with a long list of foods, including soy, salami, sauerkraut, cheese, and nuts. Common side effects of the medication include fatigue, muscle aches, insomnia, and reduced libido. MAOIs can interact dangerously with cannabis, and the combination should be avoided.

Newer Antidepressants (SNRIs)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are used to treat symptoms of depression, such as irritability and sadness. Doctors also prescribe these drugs, under the brand names Fetzima and Cymbalta, to treat anxiety disorders and nerve pain. SNRIs work by blocking the reuptake of both serotonin and norepinephrine.

Potential Side Effects

Frequent side effects of SNRIs include dry mouth and excessive sweating. SNRIs are relatively safe for most people, and they pose a low–moderate risk of negatively interacting with cannabis.

Risk Factors of Combining Cannabis With Antidepressants

Combining cannabis with antidepressants poses several risks. The herb produces the most dangerous outcomes when combined with tricyclics and MAOIs. However, it may be safe to smoke while taking newer medications such as SSRIs.

You should always consult your physician before combining cannabis with any antidepressant to ensure you’re making a safe decision that won’t put your life in danger. Depending on your personal and family history, among other factors, your risk of having an adverse reaction could be more or less likely.

Does Cannabis Interact With Other Mental Health Medication?

Cannabis may also interact with the common anti-anxiety drug class benzodiazepines (e.g. Xanax). Although no research documents any interaction between the two substances, both work as central nervous system depressants. Moreover, both substances may help to ease feelings of nervousness when taken in low doses, while high doses may give rise to paranoia and rapid heart rate.

Mixing Xanax and cannabis may result in side effects such as dizziness, drowsiness, trouble concentrating, slurred speech, and confusion. Cannabis can also interact with other mental health medication, including sedatives such as Ambien.

What About CBD and Antidepressants

CBD poses a relatively high risk of interacting with antidepressants. Although the cannabinoid doesn’t produce psychotropic effects, it does cause shifts in brain chemistry and liver metabolism. CBD can slow down how fast the liver processes antidepressants, causing elevated levels to circulate around the body. Discuss CBD with your doctor before combining it with antidepressants to make sure you do so safely.

Can You Mix Cannabis and Antidepressants?

Yes and no. Some antidepressants cause dangerous interactions with cannabis; others are relatively safe to take at the same time. Ultimately, you should consult a healthcare professional if you wish to use cannabis and antidepressants together. The combination may provide enhanced results, but you need to ensure you’re being as safe and responsible as possible.

Both cannabis and antidepressants are used by people with depression. However, taking them at the same time requires careful consideration. Find out more.

Effective Medication to Treat Bipolar Disorder

Q1. My 22-year-old son has been diagnosed with a mild case of bipolar disorder. A psychiatrist prescribed Lamictal (lamotrigine; 300 mg daily). After one year, my son felt it was not helping him and caused his hands to shake. He slowly discontinued the medication and is now self-medicating by smoking marijuana a couple of nights a week. He tells me that it has a calming effect and that he sleeps better. What do you know about pot and bipolar disorder?

There is a very high rate of substance abuse among people with bipolar disorder. Probably this is no accident, because drugs like marijuana can be a means of self-medication, of escaping unpleasant bipolar symptoms, including anxiety and depression.

Unfortunately, marijuana is not an effective solution. While it doesn’t typically become physiologically addictive, as do cocaine and heroin — that is, marijuana doesn’t cause physical symptoms of withdrawal when you stop using it — it is highly psychologically addictive. Long-term complications of chronic marijuana use include problems with memory and concentration, apathy (a lack of motivation and emotion), reduced libido, and loss of interest in other activities. Because of this, using marijuana frequently is probably sapping your son’s motivation to get effective treatment for his bipolar disorder and lead a productive life. Over time, he’ll need to use more to achieve the same effect.

I highly recommend that your son get back into active treatment for bipolar disorder with a psychiatrist or psychologist — the doctor can also help him determine whether specialized treatment for marijuana addiction is indicated.

Q2. I’m on various meds for bipolar I. I was recently told by my doctor that my triglycerides are very high because of the medications I’m taking (she put me on Tricor/fenofibrate). She suggested I come off some of them but could not tell me which ones. As of right now, I am pretty stable with what I’m taking, but I fear a relapse should they take me off meds. What do you suggest I do? She suggested I have a consultation with an endocrinologist and/or a psychiatrist, so they could tell me which ones to come off. I have to schedule an appointment. In the meanwhile, these are my meds: Seroquel, Abilify, Lamictal, Lexapro, Wellbutrin, Lunesta (eszopiclone), Chantix (varenicline), and Ritalin (methylphenidate). Do you know which ones could cause extremely high triglycerides? Do you know which ones could cause blood sugar issues? Thank you for your time.

Certain atypical anti-psychotics – particularly olanzapine and clozapine, but also Seroquel (quetiapine), which you are currently taking – have been associated with elevated triglyceridelevels, as well as elevated levels of sugar in the blood, which can lead to a state of insulin resistance. These adverse side effects may be related to an increased risk of developing adult-onset (type 2) diabetes in people taking these medications.

While there are some anecdotal reports of elevated triglycerides associated with Lamictal (lamotrigine), this is not a common side effect of this drug or the other medications you are taking. So, my first rough guess would be the Seroquel. However, there could also be complex medication interactions that are causing the problem, particularly given the number of medications you are taking.

It’s important that you discuss the target symptoms of each of these medications with your treating physician. For example, why did he/she prescribe two different atypical anti-psychotics (Seroquel, Abilify/aripiprazole) and two different anti-depressants (Lexapro/escitalopram, Wellbutrin/bupropion)? It sounds like coming off of some of these would be a good idea, for a variety of reasons. The first step is to understand what each of these medications is doing for you. You can do some of your own research by using drug databases on the Web, but you should definitely discuss this with your prescribing physician.

Q3. I am a 35-year-old woman with bipolar disorder who wants to become pregnant. I am currently taking Seroquel 300 mg, one pill every night before bed. I am aware that this drug is a class C drug, which may or may not cause damage to the unborn child. With this in mind, what are some other class A or B medications I could take temporarily while trying to conceive and during pregnancy?

This is a question which definitely needs to be addressed with your prescribing physician. There is considerable controversy about the relative risks and benefits of taking anti-depressant medications during pregnancy. To my knowledge, there are only individual case studies on the safety of Seroquel (quetiapine) during pregnancy (as opposed to large-scale studies). While there is no clear evidence of adverse effects on the fetus, clearly more information is required regarding both safety of use during pregnancy, as well as the long-term effects on children exposed to class C drugs in utero.

Generally speaking, drugs in either class A or B are considered safe and are routinely used. However, there may be exceptions. The American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice recently issued a consensus opinion regarding the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. It states that while numerous studies have not found an increased risk of major birth defects associated with the use of SSRIs during pregnancy, their use should be carefully considered for each patient, based on the relative risks and benefits.

In addition, there is some unpublished data suggesting that the use of Paxil (paroxetine) during the first trimester of pregnancy may be associated with an increased risk of congenital heart malformations. Among mood stabilizers, lithium consistently shows minimal risks to the fetus, although some anti-convulsants (such as Depakote/divalproex and Tegretol/carbamazepine) have been proven harmful to fetuses, possibly contributing to neural tube defects and other birth defects.

Q4. I have been living with bipolar disorder, untreated, for the last 15 years. Will I have a shorter life expectancy because of this?

Your question is very challenging because I have such limited information about you. The best answer I can offer is a qualified “I don’t know.”

It is complicated, because I don’t know how you have lived these last 15 years. I don’t know if you have bipolar I or bipolar II disorder. I don’t know if your symptoms have been severe enough to impair your social and occupational functioning, or if you have attempted suicide. I don’t know if you have been able to maintain a job that comes with health care benefits, or how many times you have been married or divorced. I don’t know if you smoke, abuse alcohol or drugs, have unprotected sex, or go on gambling binges. I don’t know if you have annual physicals. I don’t know how often you go for long periods of time with little or no sleep, or if you have experienced psychotic episodes.

I do know that the items listed above — whether directly or indirectly — have all been shown to contribute to early mortality. So, if you can respond favorably to the above items, then you have not experienced significant negative consequences of your untreated bipolar disorder. And that would be a very fortunate thing.

Q5. I have been successfully treated for bipolar disorder for the past five years. I take my meds (Prozac/fluoxetine and Neurontin/gabapentin) faithfully. I know bipolar disorder has no cure; however, I’m wondering if it would be possible for me to gradually be weaned off the meds. I am able to take a lower dosage of the Neurontin than I previously took. I was first treated with Depakote (divalproex) following a psychotic episode that resulted from misdiagnosis and incorrect meds. The Depakote made me feel zombie-like. With the Neurontin and Prozac, I’ve had to also take Adderall (amphetamine-dextroamphetamine) to keep from feeling scatterbrained. I guess I also have attention deficit disorder. Should I just count my blessings and continue these three meds for the rest of my life? Thanks.

It is certainly possible to gradually discontinue medications, with very careful monitoring by a good physician. The important thing to keep in mind is that it should be gradual, and done according to a specific plan made with your doctor. Don’t attempt this on your own!

If your symptoms start to recur once your dosages have been substantially reduced or discontinued, don’t be too disappointed – you may just need to maintain a minimal dosage of a mood stabilizer or anti-depressant, but you should not assume you need to be on those medications for the rest of your life.

Q6. My brother has recently been diagnosed with bipolar disorder. Are there any other drugs to treat it besides lithium? Also, can manic depression be caused by excessive drug abuse (he’s just recently been put in rehab) or is it just something that you’re born with?

There are many other medications which effectively treat bipolar disorder, the most common of these are valproate (Depakote), carbamazepine (Tegretol) and lamotrigine (Lamictal), which can be prescribed as single-drug therapy or in combination with other medications. Although lithium happens to be the oldest medication for bipolar disorder, it also remains one of the most effective. (The links below have more information about the medicines mentioned here.)

Currently, there is little evidence that manic depression can be caused by excessive drug abuse in the absence of a genetic predisposition to the disorder. However, bipolar disorder and substance abuse (particularly alcohol abuse) frequently occur together, and drug or alcohol abuse can certainly contribute to mood instability, particularly in vulnerable individuals. In some cases, bipolar disorder clearly develops before the substance abuse begins; but in others, it’s not so clear which came first.

Nevertheless, when bipolar disorder and drug or alcohol abuse co-occur, each can worsen the severity of the other, and can complicate treatment efforts for both conditions. So it is very important that treatment addresses both conditions.

Q7. I have manic depression and take 20 mg of Lexapro. I would like to get off the prescription and take natural vitamins instead. What vitamins should I take, and how much would I need?

While some people with bipolar disorder have been able to successfully reduce their medication dosages or even discontinue them altogether, this is not something I would recommend to anyone unless it is done with very careful monitoring by a physician or psychiatrist.

First, what are the reasons that you would like to stop taking your medication? Of course, there are plenty of reasons I can imagine why you may be motivated to try this switch. I suggest you discuss your goals of discontinuing Lexapro (escitalopram) with your doctor, and if he or she deems it appropriate, you can gradually decrease the dosage. The other important thing to note is that abrupt discontinuation of Lexapro frequently results in some adverse “withdrawal” effects, so gradual dose reduction is advised. Another consideration is whether you are only taking Lexapro or if you are taking it in combination with a mood stabilizer. There would need to be a good reason why you would not be taking a mood stabilizer, such as if you had very mild symptoms of mania and/or very few episodes of mania. Otherwise, the typical primary treatment for bipolar disorder is mood stabilizers, sometimes in combination with antidepressants.

In terms of which herbal remedies you should try, St. John’s wort has probably been the best researched as an antidepressant. While there is some evidence that it’s effective in treating milder depressions, it doesn’t appear to work as well for severe depression. I am not aware of any published studies on its effectiveness in treating bipolar disorder. Kava, valerian root and ginkgo biloba are other herbal remedies commonly used to treat mood symptoms, although again, there are no published data on their effectiveness in treating bipolar disorder.

If you do decide to try herbal remedies, make sure to pick a brand with high quality control and keep track of your symptoms to see whether or not it’s working. However, keep in mind that no herbal remedies or supplements are approved by the Food and Drug Administration, and that they may also have adverse side effects. You can read more about clinical studies of herbal medicines in “The Handbook of Clinically Tested Herbal Remedies” By Marilyn Barrett, Ph.D.

Q8. I don’t know what is happening to me. In the last year all things have changed for me. I have gained 50 pounds, I sleep almost 18 to 20 hours a day, I have hot flashes all the time, I can’t remember things, I can’t think, I have quit my job with no income, and my boyfriend has moved in with me but I attempted suicide twice because of his actions. I cannot get back to me. Approximately a year ago I changed some meds. The most was changing from Effexor (venlafaxine) to Cymbalta (duloxetine). Could this one drug change have all of these effects on me? I have been checked for perimenopause and thyroid problems and all came back normal. I am at a loss.

It is surprising that this single medication switch could have such a profound effect, but it sounds like — regardless of the causes — Cymbalta is not working well for you. What were the reasons for the medication switch? I ask because the evidence for Cymbalta’s effectiveness for depression is not overwhelming. A meta-analysis of placebo-controlled trials, published earlier this year in the New England Journal of Medicine, concluded that the effect size of duloxetine as compared with placebo was weak to moderate, and similar to other 11 anti-depressants studied.

While the difficulties you’re describing would not be common side effects, you might consider a medication switch. Based on the symptoms you are describing, I would also suspect thyroid and/or perimenopause, so it is good you got this checked.

Also, you don’t mention whether Cymbalta is the only medication you are taking or if this is just one of several. Weight gain can be associated with some of the medications prescribed for bipolar disorder. Are you taking a mood stabilizer in addition to the antidepressant? Mood stabilizers are usually the cornerstone of bipolar treatment.

It sounds like you are feeling things spiraling out of control right now, and so the best thing for you to do would be to discuss your current treatment plan with your doctor. A medication switch may be helpful but I would highly recommend psychosocial therapy as well, if that is not already part of your treatment.

Q9. My psychopharmacologist, Dr. X, took me off many unnecessary medications this past spring, and he’s reduced the dosage of the last two, Topamax (topiramate) 200 mg at night (I formerly was taking 300 mg morning and night) and Seroquel (quetiapine) 50 mg. I have maintained stability and perfect mental health now for 21 weeks, since the end of the longest and severest depression I ever experienced. Do you think, as I do, that Dr. X should wean me off the remainder of Topamax and Seroquel before Daylight Savings ends this autumn? Thank you; I truly appreciate this.

I am glad to hear you are doing so much better now. However, if the worst depressive episode you have ever experienced ended just 21 weeks ago, it may be premature to discontinue all medications this soon.

Why is the end of Daylight Saving Time your deadline? If your depression tends to have a seasonal pattern it might be a problem to stop taking your medications while the days are getting shorter. But certainly, if this is something you feel strongly about, the important thing is that your mood symptoms are monitored very closely. You may wish to keep a daily log to track your symptoms over time, so you can see how reducing or discontinuing your medication is affecting things.

Q10. Is it fair that I have asked to be taken off of Geodon and put on Topamax or another mood stabilizer and my doctor will not agree? He assumes I might get manic, but my opinion is if I am on a mood stabilizer, that won’t happen. I dislike Geodon and the long-term side effects.

It is critical to have a good working relationship with your doctor. It sounds like he has some legitimate concerns about the possible implications of switching medications. Although Topamax (topiramate) is an approved treatment for seizure disorders and migraine, it is now commonly prescribed for bipolar disorder, often in addition to other medications.

What are the long-term side effects of Geodon (ziprasidone) that trouble you? It is possible that your doctor does not really understand the reasons you dislike your current medications. If you clearly have researched the issues and can document exactly why you feel like a medication switch would be beneficial for you, your doctor is more likely to listen. Hopefully this strategy will be helpful in finding a solution that works well for both of you.

"My 22-year-old son has been diagnosed with a mild case of bipolar disorder. He is self-medicating by smoking marijuana. What do you know about pot and bipolar disorder?"