Can You Take Cbd Oil And Buspirone Together – Travelmax Best Can You Take Cbd Oil And Buspirone Together, Do Cbd Gummies Work For Anxiety Cvs Cbd Oil. Whats The Strongest Strength Of Cbd Oil Cost Buspirone is mostly prescribed for anxiety but may also help with depression and other mental issues. Discover its uses, side effects & natural options. Antidepressant and Anxiolytic Effects of Medicinal Cannabis Use in an Observational Trial This is an open-access article distributed under the terms of the Creative Commons Attribution License
Can You Take Cbd Oil And Buspirone Together – Travelmax
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It s hard to say what the other members of the organization are, It won t kill innocent people. Don t worry about that, let him relax, The girl in the vest bit her lip and nodded. That s cbd fit whey right, no one is there! Originally, in addition to the village can you take cbd oil and buspirone together shark tank jolly cbd gummies chief and cbd oil benefits those who attacked the village, there were at delicious gummies least more than 20 villagers here, but now they have completely disappeared. Those fists attacked him actively, but kept walking through the valley, actively destroying the gloves on those corpses, he became more and more mad, and his state became more and more mad and abnormal, Haha, are you desperate? Are you desperate.
best cbd gummies This is enough to show that although this fist intent can improve the combat effectiveness, it is not enough to threaten the outcome of the entire battle. Otherwise, if the police s ability to solve the crisis is low, everything will be in vain. Sykes exclaimed, can you take cbd oil and buspirone together cbd gummies for sleep recommend cbd gummies reviews Go away! Bingxue Xiaohuiyue slapped out, and Sykes flew can you take cbd oil and buspirone together upside down hundreds where to get cbd gummies or oil in tampa of meters away, even when she had activated her own defense.
Well, you are awesome, you are a very special existence among S-class heroes. Speaking of this topic, Hiluda immediately The tone became much heavier. If he hit him twice gummies for sleep like this, even if he had the ability to heal himself, it would be useless, and his internal organs would cbd gummies near me be smashed to death. Brother Tomboy waved his hand, Although she is a girl, her behavior is more boyish than boys.
In a blink of an eye, appeared hundreds of meters away again, and even the purple-haired woman couldn t keep up with that speed. Moreover, there is no situation on the side of the Sword Saint Association, and there gummies price is no blessing from the Sword God, which is a can you take cbd oil and buspirone together bit strange. Over there, Xiluda s projection Can You Take Cbd Oil And Buspirone Together appeared on top of this side s head, You two, the game is about to start, let me talk about the rules first. However, the cbd side effects Institute of can you take cbd oil and buspirone together Spiritual Power best cbd seeds did not buy it, and just extended the 1 hour time to 24 hours. The heroes whispered one by one, very curious, who the driving knight will bet on, if can you take cbd oil and buspirone together it is the spring beard, then this side is equivalent to a bit gummies weaker. Several people talked about the reasons for the failure, and at the same time, they also classified the three people into the scope of using small means to play underhand tricks, and they despised them to the extreme.
person came out! However, the human in the animal skin clothes was lying on thrive cbd oil the ground. Haha, good! Nanfang Xiangjie also flipped his wrist, forcing his palm out, with a bang, right palm. At this moment, the formula swiss cbd oil review girl in the vest lowered her head and bit her swollen arm. Therefore, time was very precious, shark tank sleeping gummies You guys, don t you think it s too quiet here? He frowned. Hmph, you still look down on people like that, Today is the beginning of your capsize.
Can You Take Cbd Oil And Buspirone Together It s nothing, it s just that I suddenly understand the meaning of boxing. Hiss, The moray came out of the can you take cbd oil and buspirone together deep sea king good best cbd products s mouth, opened his mouth with cbd near me sharp teeth, and provoked Sykes and Hellblow from time to time. The question of Hellblow Snow seems very strange, because Sykes is in front of him, both in appearance and breath. Go back to find the master first, and ask just cbd gummies about the situation of this temple. With a smile, can you take cbd oil and buspirone together when he jumped into the high-altitude battle, he glanced at the does cbd oil affect blood pressure surrounding environment, and the surrounding situation was already gummies imprinted in his brain. There are enough support pillars for three people to hug, It is more than 20 meters high and supports a triangular roof. Indeed, if this matter is said, his A-level hero is increase time cbd gummies defeated by a B-level hero s subordinates. can you take cbd oil and buspirone together Each each other, His eyes locked tightly on each other s key parts, Suddenly, The other party raised his right shoulder. His scalp was a little reviews gummies mg numb, sparoom cbd oil and he found that since he accepted GG s mission to come here, one question after another became like a wave, overwhelming him. The three people left the area, and the trees did not continue to attack them.
Shaking his head, It s settled, there s no time to discuss! Just follow the redeem cbd gummies strategy I just said, remember everyone s duties, and don t make mistakes. They use this feeling to create fist intent and domain, but, If the opponent is a robot and does not have can you take cbd oil and buspirone together shark tank jolly cbd gummies the ability to cbd gummies for memory interpret this atmosphere, the effect will be much worse. Taking a deep breath, this Taoyuan can you take cbd oil and buspirone together Village is a place like a mystery, let alone such a stone gate, and, This stone gate seems to have cbd oil some power guarding it, can you take cbd oil and buspirone together and it can t move at all. 1, There are other introductions below: This experimental Can You Take Cbd Oil And Buspirone Together subject comes from the House of Evolution, and it cbd store is the masterpiece of Dr Kenos. gummies supplements Hey, let s give up, The master of Mingquan said with a smile, Fisting is all about talent. What did can you take cbd oil and buspirone together you see? Hell Fubuki approached cautiously, She didn t fully regard Sykes as her reliable partner.
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Can Cbd Oil Cure Melanoma?
Even she can you take cbd oil and buspirone together does not dare to use too much mental power in this stone, this stone is like a quagmire, as long as one of your feet sinks in, it is difficult to pull it out. At the same time, he would kill a policeman every hour! I m afraid of what s coming. Waiting for someone to nod, as for the road, there will be a map, the six people pack their bags and can you take cbd oil and buspirone together set off towards the meeting point. To break the force that temporarily bound him, You forgot, we are still cooperating! With a roar, he pushed his hands to both sides, and two punches were immediately sent out, Iron Shattered.
Ten million coins! This is an ordinary hero who can t earn money in a lifetime, no, ten lifetimes. After a commotion, the village chief coughed, and all of a sudden, everyone fell silent.
Why did you make such a decision? After speaking his thoughts again, Xiluda immediately understood his intentions. Turn on the mobile TV, Unexpectedly, a large-scale debate between the Hero Association and the police station has broken out at this time.
And now, with this punch, an inverted triangular gully was blasted directly in front. But, now comes the problem, Why do villagers turn into candy? Thinking that the plants and animals in this area have also mutated, I couldn t help shivering, thinking of an extremely terrifying result. Quickly, the rotating weed gummies force pushed inhouse pharmacy benefits of cbd oil these two mountains outward constantly. Sykes injected his mental power into the stone again, and then the stone shot out best cbd gummies a ray of light that directly thc gummies shot dozens of meters away.
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Actually, your ability is already improving, but you don t know it yet. In a quiet cafe, The two sat down, light soft can you take cbd oil and buspirone together music was playing in the cafe, and only single-digit people chatted softly inside. Because he was looking for Hajiro and his children, he went around several cities several times, and encountered cbd gummies and drug test a lot of so-called strong human beings. However, he used to think that it was normal for him to cross over and occupy this body and not inherit the other party s memory. Turn over again, Entering the building, because all the back ends of the cameras and the back end of the intrusion alarm were destroyed, although walking inside the building, it did not cause any alarm or abnormality. There is a very important reason for the large-scale release of fist intent. Therefore, she didn t feel the smell of your cbd store Bingxue Xiaohuiyue, and at that time, she When cbd oil and pancreatitis I was still young, the feeling was much lighter than the trembling tornado, and I had forgotten many memories. Mind power turns the storm? Pineapple Chuixue cbd gummies for kids near me was a little puzzled, but the opponent was a strong martial artist.
On his right, there were two people lying on duty, It was the two little policemen who were on duty today. Still have time to look around? Bang, A effective royal cbd second person was embedded in the wall, In just an instant, Pineapple Blowing Snow was completely defeated, and the opponent s strength was beyond imagination.
The girl in the vest and Saitama-kun watched at the same time, and they were stunned. We don t know, can you take cbd oil and buspirone together the village chief has been in contact with her all the time.
Is Cbd Safe With Other Medications?
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This courage and skill made me sigh inwardly, Boxing is a very magical thing. He felt Can You Take Cbd Oil And Buspirone Together powerless deeply, and he felt deeply self-blame when he saw the hero being killed like this. Could it be that the powerhouses back then were all that strong? With pure cbd oil emotion, if these guys were still alive, they would be comparable to the can you take cbd oil and buspirone together Candy Association. Pineapple Chuixue shook her head, but she had already given her a task just now, and also gave her two bottles of nutrient solution, so that she should not be stingy and replenish her energy at the right time. As gummies the so-called, deliberately planting trees will not be successful, but inadvertently planting willows and willows will make a shade.
renown cbd gummies for sale She is not a fool either, There are indeed a lot of people in the Fubuki team, but most of the time, when they fight with weirdos, these people are just gummies 2022 a constantly growing cheerleader, and there are can you take cbd oil and buspirone together not many real talents. The guy who has been dead for a thousand years is still haunted! can you take cbd oil and buspirone together The village chief cursed angrily, turned around, and pulled out from the deep pit of the rock, then grabbed his chin and let him His mouth opened, then grabbed a candy cell and wanted to stuff it into cbd oil side effects his mouth. After finishing his suit, he hoped to surprise these people, The cbd gummies for pain greater the hope, the greater the disappointment. It has a special effect, I need to get more information cbd oil acid reflux from this kind of stone. crazy, which is better for sleep pure cbd gummies or 1 1 Four-Eyed Candy rushed over like a madman, and he wanted best sleep gummies to shred it to relieve the hatred in his heart. The plan was completely bankrupt, gummy edibles He looked up at the sky, In thc gummy the sky, Shui Long hangs straight in the air, as if he has gummies mg become the master of this space, the light in that space seems to be absorbed, and only he and Bangshan are left in this world. .
5 Buspirone Uses, Side Effects, Dosage + Natural Options
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Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc. ]” means that the information is found within the full scientific study rather than the abstract.
Buspirone is a prescription medication indicated primarily for anxiety but may also be used “off-label” for depression and other mental disorders. Read on to learn the uses and side effects of buspirone + natural complementary approaches to anxiety.
Disclaimer: This post is not a recommendation or endorsement for buspirone. This medication is only FDA-approved for the treatment of certain specific medical disorders, and can only be taken by prescription and with oversight from a licensed medical professional. We have written this post for informational purposes only, and our goal is solely to inform people about the science behind buspirone’s effects, mechanisms, and current medical uses.
What is Buspirone?
Buspirone is an anti-anxiety medication (anxiolytic) that is sold under the brand name Buspar. It is chemically and pharmacologically distinct from other anti-anxiety drugs such as benzodiazepines and offers reduced anxiety without physical dependence or withdrawal symptoms [R, R].
Buspirone is most commonly used for generalized anxiety disorder but is also prescribed occasionally for anxiety related to other brain-related disorders such as depression, attention deficit disorder, social phobia, Parkinson’s disease and Alzheimer’s [R, R].
Mechanism of Action
The mechanism of action of buspirone is not fully understood. It is known that buspirone binds to serotonin (5-HT1A) receptors and partially mimics the action of serotonin. Serotonin is a chemical in the brain that promotes feelings of well-being and happiness [R, R].
Buspirone is also able to partially block the action of some dopamine receptors (DRD2) [R, R].
When buspirone is broken down by the body, one of the major byproducts called 1-PP becomes quite concentrated in the blood. 1-PP can block the activity of a receptor that epinephrine/adrenaline activates (α2-adrenergic), which could account for some of the anti-depressant effects of buspirone [R, R, R, R].
When taken by mouth (20 mg) it is rapidly absorbed and reaches its peak concentration within the blood in less than an hour. It takes 2.5 hours for half of the initial dose to be removed from the body (half-life). However, like most anti-anxiety medications, it may take 3-4 weeks until you start to feel relief from symptoms [R, R].
Approved Medical Uses
Buspirone treatment is more effective than placebo in treating and maintaining stability for generalized anxiety disorder (GAD) based on a ten-week trial in 125 patients [R].
GAD is persistent, uncontrollable worry that requires professional therapy or medication to be resolved [R, R].
Buspirone is as effective as benzodiazepines, such as diazepam or lorazepam for treating generalized anxiety. This was shown in a study of 367 menstruating female patients, and 2 studies with 84 adults [R, R, R].
It is equal to or better (after 2 and 4 weeks) than sertraline (an SSRI) for GAD, based on a study of 46 people [R].
Based on the above results, the FDA has officially approved buspirone for the treatment of generalized anxiety.
Occasionally, doctors will prescribe drugs like buspirone to help treat conditions that fall outside of the official uses approved by the FDA – also known as “off-label” drug use. Usually, this is done because there is actually decent evidence that the drug may help, although not enough to get full FDA approval [R].
However, keep in mind that the decision to use medications in this way can only be made by a licensed medical professional.
Buspirone is more effective for treating major depressive disorder than placebo, based on a meta-analysis looking at the results of 15 randomized controlled trials with a total of 2,469 patients [R].
Two large studies performed in 300 adults for 8 weeks with both major depression and moderate anxiety resulted in significant improvement in symptoms for a majority of treated patients [R, R].
Taking buspirone for 8 weeks improved major depression in 61% of 177 elderly patients (double-blind randomized controlled trial) [R].
A randomized study of 286 adults being treated for depression with citalopram, found that augmentation with 60 mg/day buspirone resulted in a 30% remission rate based on the Hamilton Rating Scale for Depression [R].
Buspirone increases cortisol secretion (via 5HT1A), which may improve depressive symptoms [R].
3) Substance Abuse
The use of buspirone to help overcome substance abuse has had somewhat disappointing results, as conflicting data have been published for substance abuse of many types.
Buspirone was useful in helping high anxiety patients stop smoking in a study with 101 people. Participants that were considered to be low anxiety did not experience any benefit from taking buspirone [R].
However, it did not help 35 crack cocaine users (60 mg/d) in their addiction [R].
The effects of buspirone treatment on marijuana dependence have been conflicting. One study of 50 adults found it helped, while it didn’t with another study of 175 people [R, R].
Buspirone did not help methamphetamine use in 8 participants [R].
In primates, buspirone was found to be helpful in reducing nicotine and cocaine addiction [R].
Other Potential Uses
Buspirone has also been studied for other health conditions. However, keep in mind that the evidence supporting these potential applications is still only preliminary, and a lot more additional research will be needed before any of these applications are approved. Therefore, take all of the information below with a grain of salt.
4) Sexual Risk-Taking in Cocaine Users
There is an association between cocaine use and sexually transmitted diseases that are attributed to an increase in sexual desire and a decrease in self-control when using cocaine. Buspirone improves impulse control in rats and reduced the reinforcing effects of cocaine in preclinical trials [R, R].
Nine cocaine users were treated with 30 mg/day of buspirone for 3 days (repeated measures, inpatient protocol). Buspirone did not interact negatively with cocaine and users were found to be more likely to use a condom [R].
However, a placebo-controlled study of 11 cocaine users found no effect of buspirone on impulse control, but only a slower reaction time at the very highest dose tested (30mg) [R].
Chronic administration of buspirone has some beneficial effect on impulse control in both rodents and non-human primates [R, R, R].
5) Symptoms of Developmental Disorders
In a study of 166 children with autism, ages 2 to 6, small doses of buspirone (2.5 mg) helped alleviate repetitive behaviors [R].
In 40 kids with autism, low doses of buspirone in combination with an antipsychotic (risperidone) resulted in significantly decreased irritability [R].
A case study reported decreased hyperactivity and an increased ability to complete performance tasks in a child with autism [R].
Buspirone Side Effects & Safety
A meta-analysis 289 patients found that the most common side effects are dizziness, headache, and nausea [R].
Patients generally do not experience drowsiness, weakness, fatigue or depression as is common with other anti-anxiety medications [R, R, R].
There are some anecdotal reports of Buspirone causing weight gain, but there are no clinical reports that back this claim. A pilot study on 6 schizophrenic patients actually observed weight reduction for patients switching to buspirone from olanzapine or risperidone (which are known to cause weight gain) [R].
The following are other potential side effects reported on various sites, but they are not found in the scientific literature:
- blurred vision
- dry mouth
- upset stomach
- stuffy nose
- sore throat
- ringing in the ears
Drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before taking any drug and let them know about all drugs and supplements you are using or considering.
A study in 10 healthy volunteers found that taking buspirone in combination with grapefruit juice significantly increases the blood concentration of the drug, and should be avoided when taking this prescription medication [R].
There is a reported case study of serotonin syndrome in an individual taking buspirone and linezolid concomitantly. Consult your doctor before combining buspirone with other anti-anxiety or anti-depression medications [R].
A study performed in 24 healthy men found that alcohol (0.8 g/kg) and buspirone had little additive effect on intoxication and in some cases, buspirone seemed to reverse the effects of alcohol [R].
Another study in 12 young males found no interaction between buspirone and alcohol. However, alcohol affects everyone differently, so it’s extremely important to take caution when combining alcohol and prescription medications [R].
- Buspirone hypersensitivity.
- MAO-inhibitors (antidepressants) within 14 days due to increased risk of serotonin syndrome and/or elevated blood pressure.
Pregnancy and Breastfeeding Considerations
Buspirone has a category B risk in pregnancy. In general, there are no definitive studies that have shown buspirone to be a risk to the fetus. However, caution is always advised if you are going to take the medication while pregnant, and the benefits of taking the medication should be weighed versus any potential risk to the fetus.
Please speak to your doctor or a qualified healthcare professional. It is not known if buspirone is transferred to breast milk, but it is advised to not take it if you are breastfeeding [R].
Buspirone Forms and Dosage
The below doses may not apply to you personally. If your doctor suggests using buspirone, work with them to find the optimal dosage according to your health condition and other factors.
Buspirone is available in 5 mg, 7.5 mg, 10 mg, 15 mg, and 30 mg tablets, and is commonly taken at 15 mg/day for treatment of anxiety (divided into 2 or 3 doses), but the dosage is dependent on indication and clinical trials have found it is well tolerated up to 90 mg/day [R, R, R, R].
Buspirone is generally thought to have a more ideal side-effect profile than benzodiazepines. There is only a single report of buspirone overdose causing a seizure in a human, although there are additional animal model reports of this happening [R].
Buspirone vs. Xanax
Buspirone improves anxiety by acting on serotonin receptors in the brain, while Xanax alters the effect of GABA, another neurotransmitter. Buspirone does not have sedative, muscle relaxant or anti-convulsive effects that benzodiazepines such as Xanax have. Additionally, Buspirone has a much smaller potential for abuse and minimal withdrawal symptoms [R].
CYP enzymes are responsible for breaking down or metabolizing drugs that enter the body. Buspirone is metabolized by CYP3A4, so mutations in this enzyme could change how buspirone is processed and how it affects you. Specifically, the T variant of the rs35599367 SNP is associated with decreased enzymatic activity in the liver, which could lead to higher drug levels in the bloodstream [R].
Natural Complementary Approaches
In most cases, complementary approaches cannot permanently resolve a diagnosed anxiety disorder. If you have one, make sure to precisely follow your doctor’s recommendations. That being said, supplements and lifestyle changes discussed below may improve the effectiveness of conventional treatment options.
Exercise has been shown in numerous studies to be effective for reducing anxiety. Aerobic exercise, such as running, biking or hiking, is most effective. Similar to buspirone, exercise reduces anxiety by increasing beneficial neurotransmitters such as serotonin, dopamine, norepinephrine, and endorphins [R, R, R, R, R, R].
A large proportion of people with anxiety have also been found to have GI disorders and evidence for a link between the gut microbiota and brain function is quickly growing. More specifically, the gut microbiota is being shown to play an important role in Serotonin production [R, R, R, R].
Like buspirone, increasing the health of your gut-flora by supplementing with probiotics can improve serotonin transmission and help reduce anxiety. The following strains have been specifically shown to improve psychological health:
3) 5-Hydroxytryptophan (5-HTP)
5-Hydroxytryptophan (5-HTP) is an over the counter supplement that is a precursor to serotonin. Similarly to the way that buspirone treats anxiety by boosting serotonin activity, supplementing with 5-HTP has been shown to reduce anxiety and panic attacks in humans [R, R].
4) Cannabidiol (CBD)
CBD is a component of hemp that is non-psychoactive and has many proven health benefits. CBD has been shown to reduce anxiety in both healthy patients and those that have been clinically diagnosed with social anxiety disorder. CBD interacts with the same serotonin receptors (5-HT1A) as buspirone [R, R, R, R].
Keep in mind that CBD may not be legal in your country. Check with your doctor if CBD would be a legal and potentially effective addition to treatment.
Ashwagandha is an Indian herb that helps to restore hormonal imbalance and improve immune function. It has been shown in humans to help stabilize mood fluctuations and has proven anti-anxiety effects in animal models [R, R, R, R].
Based on a study in mice, the anti-anxiety effects of ashwagandha could be due to a resulting increase in both GABA and serotonin [R].
6) Lemon Balm
Lemon balm is an herb commonly consumed as a tea that has been shown in several small human trials to reduce anxiety. A study performed in rats suggests that lemon balm may increase the activity of serotonin, similar to the effect of buspirone [R, R, R, R, R].
7 ) Lavender
Lavender is a flowering plant with a pleasant smell that is often associated with calmness and sleep. Silexan is an oil derived from lavender that can be taken by mouth. Clinical trials in humans have shown that Silexan can reduce anxiety in patients with post traumatic stress and anxiety disorders [R, R, R].
Animal studies have shown that similarly to buspirone, the serotonin system plays an important role in the anti-anxiety effects of lavender oil [R, R].
Antidepressant and Anxiolytic Effects of Medicinal Cannabis Use in an Observational Trial
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The datasets presented in this article are not readily available because the corresponding author does not own this data. Requests to access the datasets should be directed to Ryan Vandrey ([email protected]).
Background: Anxiety and depressive disorders are highly prevalent. Patients are increasingly using medicinal cannabis products to treat these disorders, but little is known about the effects of medicinal cannabis use on symptoms of anxiety and depression. The aim of the present observational study was to assess general health in medicinal cannabis users and non-using controls with anxiety and/or depression.
Methods: Participants (368 Cannabis Users; 170 Controls) completed an online survey assessing anxiety and depressive symptoms, cannabis product use, sleep, quality of life, and comorbid chronic pain. Participants that completed this baseline survey were then invited to complete additional follow-up surveys at 3-month intervals. Baseline differences between Cannabis Users and Controls were assessed using independent-samples t-tests and generalized linear mixed effects models were used to assess the impact of initiating cannabis product use, sustained use, or discontinuation of use on anxiety and depressive symptoms at follow-up.
Results: Medicinal cannabis use was associated with lower self-reported depression, but not anxiety, at baseline. Medicinal cannabis users also reported superior sleep, quality of life, and less pain on average. Initiation of medicinal cannabis during the follow-up period was associated with significantly decreased anxiety and depressive symptoms, an effect that was not observed in Controls that never initiated cannabis use.
Conclusions: Medicinal cannabis use may reduce anxiety and depressive symptoms in clinically anxious and depressed populations. Future placebo-controlled studies are necessary to replicate these findings and to determine the route of administration, dose, and product formulation characteristics to optimize clinical outcomes.
Anxiety and depressive disorders are highly prevalent (1), recurrent (2, 3), and can have a substantial negative impact on quality of life (4). Outcomes are worsened in the likely incidence of comorbidity (5–7), and both depression and comorbid anxiety/depression are associated with increased risk of mortality (8), particularly in people with co-occurring chronic physical illnesses (9). Yet, treatment is often not pursued despite the availability of multiple treatment options (6, 10–13).
Several pharmacotherapeutic interventions show efficacy in the treatment of anxiety and depression (14, 15). However, many patients are skeptical about the use of medication (16, 17), and antidepressants, the most frequently prescribed of these medications (18, 19), are not without contraindications. Adverse events are fairly common across antidepressant drug classes, and can disincentivize initiation and contribute to discontinuation of pharmacotherapy (14, 20–24). Further, although antidepressants are demonstrably superior to placebo at alleviating symptoms of both anxiety and depression, effect sizes are small (14, 25), and, thus, may not always be perceptible at the patient level. Finally, discontinuation of antidepressant treatment after sustained use is associated with a withdrawal syndrome in most patients that ranges in severity and can last for several months (26). Taken together, even though there is clear evidence of efficacy for antidepressants at the population level, perceived variability in cost-benefit ratio at the patient level means many people with anxiety or depression are interested in alternative options.
In this vein, an increasing number of people struggling with anxiety and/or depression are trying cannabis products for symptom management (27–29). Cannabis products can generally be separated into three “chemotypes” based on the predominant chemical constituents: (1) Δ9-tetrahydrocannabinol (THC) dominant products, (2) cannabidiol (CBD) dominant products, and (3) products that contain roughly equal amounts of both THC and CBD. Published studies on the impact of cannabis use on anxiety and depression have shown mixed results, and often vary based on the chemotype of the product under investigation and the duration of the dosing regimen. For example, the two studies in which THC was acutely administered to people with clinical anxiety showed limited evidence of anxiolysis (30, 31), but chronic nabilone (oral synthetic THC analog) administration over 4 weeks was associated with a significant reduction in anxiety in a placebo-controlled trial (32). Differential effects of cannabinoid type 1 receptor (CB1R) agonists, like THC, observed in long-term vs. acute dosing studies may be a product of increased CB1R binding on cortical glutamatergic neurons due to CB1R downregulation on GABAergic terminals (33, 34); a similar mechanism is implicated in the dose-dependent effects of acute THC exposure on anxiety (33). Neuroplasticity following extended exposure may also explain anxiogenesis frequently reported in cannabis withdrawal (35).
Effects of THC treatment on depression also appear mixed, though no clinical trials have been conducted to examine a direct effect of THC on depressive symptoms. Epidemiological studies suggest that non-medicinal (“recreational”) use of cannabis, which is typically THC-dominant, may be associated with increased risk of developing a depressive disorder (36) and greater depressive symptom severity (37), an association not observed for anxiety disorders (38). Rather than being causative, however, non-medicinal cannabis use may instead represent an attempt at self-medication during a prodromal period. Indeed, the CB1R agonist activity of THC mimics endogenous cannabinoid signaling, which is notably downregulated in women with clinical depression (39), and endogenous cannabinoids appear to regulate neural serotonergic signaling (40). THC itself can produce feelings of euphoria (41), and clinical trials of a CB1R antagonist were discontinued following reported increases in depression and suicidality (42). However, THC has shown no evidence of antidepressant efficacy when assessed as a secondary outcome in treatment trials for chronic pain, though self-reported depression scores in these trials were already low at baseline (43–45).
CBD, a phytocannabinoid that lacks the abuse liability of THC (46), has potential for therapeutic use in psychiatry. CBD has shown anxiolytic efficacy both acutely [(47, 48) but see (31)] and following chronic treatment in people with clinical anxiety (49). Preclinical evidence suggests that anxiolytic effects are produced via 5-HT1A receptor agonism in both acute (50–52) and chronic dosing models, without impacting 5-HT1A receptor expression (53). This lack of neural remodeling may explain why CBD discontinuation does not appear to produce a THC-like withdrawal syndrome (54). Additionally, the proposed serotonergic mechanism of CBD is distinct from that used by most common antidepressant medications, which selectively inhibit cellular reuptake of serotonin and/or norepinephrine (SSRIs, SNRIs), and is instead more comparable to the anxiolytic medication buspirone (55). Like CBD, buspirone does not appear to produce a withdrawal syndrome (56). Antidepressant effects of CBD have also been consistently demonstrated preclinically following both acute and chronic administration (57–60), though no clinical trials have yet been published. Antidepressant effects appear to be a product of the same serotonergic mechanism that drives anxiolysis (57, 58), and have been shown to synergize with other serotonergic medications (61). This again draws comparison with buspirone, which shows evidence of efficacy both as a depression monotherapy (62) or as an adjunct treatment to SSRIs (63).
Research evaluating the anxiolytic or antidepressant effects of products with a more balanced THC:CBD ratio is limited. Some studies in humans indicate that concurrent CBD/THC administration attenuates anxiogenic effects produced by THC (64, 65), but this has not been observed consistently (66, 67) and may be dose-dependent (68). This inconsistency is mirrored in the preclinical literature (69–71), making it difficult to determine a responsible mechanism given the diverse pharmacological activity of CBD (72, 73). Balanced THC:CBD products have also not been assessed for efficacy in psychiatric populations, though effects on anxiety and depression have been reported as secondary outcomes in clinical trials for other conditions. Nabiximols produced no effect on symptoms of anxiety or depression in people with multiple sclerosis (74) or in people with chronic pain due to cancer (75). Notably, both of these studies listed current psychiatric diagnosis as exclusion criteria, making it difficult to extrapolate these outcomes to people with clinical anxiety or depression.
Given these conflicting outcomes, the impact of medicinal cannabis use on anxiety and depression remains an open question. Our group previously found that medicinal cannabis users reported reduced anxiety and depression when compared to a control group that was considering, but had not yet initiated medicinal cannabis use (76). This impact of cannabis use was observed both cross-sectionally and longitudinally. However, effect sizes were only modest, and this was likely a product of the diverse array of clinical conditions represented in the sample. The purpose of the current study was to extend prior findings by limiting our focus to only participants that reported having anxiety and/or depression. We also expand on other epidemiological work that has principally focused on the impact of non-medicinal cannabis use on symptoms of anxiety and depression by providing insight into the effects of medicinal cannabis use on these symptoms.
Materials and Methods
The analyses herein represent a subsample of participants that were enrolled in the parent study between April 2016 and July 2020 (76). Briefly, the parent study was a collaboration between Johns Hopkins University School of Medicine (Baltimore, MD) and the Realm of Caring Foundation (Colorado Springs, CO), and comprised a series of online surveys (Qualtrics, Provo, UT). Participants were recruited from the Realm of Caring patient registry and via social media advertisements. Those interested in participating were provided with a unique identification number, a study overview, and instructions for survey completion. Those interested in enrolling provided informed consent before beginning the baseline survey. Upon completion of the baseline survey, participants were invited to complete additional follow-up surveys at 3-month intervals. Compensation for completing each survey was entry into a monthly drawing for a $50 gift card. All procedures were approved by the Johns Hopkins IRB.
Study participants were people that completed the baseline survey and reported having anxiety and/or depression (n = 538). Participants were included if they were at least 18 years old and endorsed having major depressive disorder, postpartum depression, dysthymia, premenstrual dysphoric disorder, seasonal affective disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, and/or agoraphobia. Participants that did not list a specific disorder and instead only endorsed “anxiety” or “depression” were also included. Of this sample, n = 368 participants reported current use of medicinal cannabis products at baseline (“Cannabis Users”), and n = 170 were considering the use of medicinal cannabis, but had not yet initiated use (“Controls”). Follow-up assessments were offered every 3 months after enrollment until the study closed in July 2020, and participants could complete as many as desired. Of the participants that completed the baseline survey, n = 211 completed at least one follow-up assessment (n = 145 Cannabis Users; n = 66 Controls), and the average number of completed assessments for these participants was 2.2 (median = 1). Follow-up assessments were recorded at an average of 14 months (SD = 9) post-baseline, and the longest follow-up occurred 44 months after baseline. All follow-up assessments completed were included in longitudinal analyses.
Surveys included validated self-report questionnaires and investigator-developed measures of health outcomes. Participants self-reported demographic information and any current medical condition(s). Medicinal cannabis use was evaluated using both multiple choice and free-response items pertaining to current use of medicinal cannabis, cannabis product type (e.g., dried flower, hemp extract oil), chemotype (e.g., THC-dominant, CBD-dominant, and balanced THC:CBD ratio), product dosing regimen, and product route of administration. Information pertaining to current use of prescription medication(s) was also collected.
Current symptoms of depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS) (77), in which a score ≥ 8 on either subscale indicates clinical concern. The abbreviated version of the World Health Organization Quality of Life assessment (WHOQOL-BREF) was used to assess perceived quality of life, health satisfaction, and mood (78). Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) (79), as sleep dysfunction is a symptom of both anxiety and depressive disorders (80). Consistent with epidemiological reports (81), chronic pain disorders were highly prevalent in this sample. Thus, recent pain was also assessed using the Numeric Pain Rating Scale (NPRS) (82). The free-response question “How has the therapeutic use of cannabis/cannabinoids harmed the participant?” provided participants with the opportunity to disclose any adverse effects of cannabis use.
Descriptive statistics were used to summarize participant demographics, cannabis use patterns, and qualitative effects of cannabis use. Demographic differences by cannabis use were evaluated using independent samples t-tests (continuous measures) or Fisher’s exact test (dichotomous measures). Independent-samples t-tests were used to assess baseline differences between Cannabis Users and Controls on the depression and anxiety subscales of the HADS, overall sleep quality score on the PSQI, past-month average and worst pain on the NPRS, and components of the WHOQOL-BREF. Independent-samples t-tests were used for these baseline, cross-sectional analyses given the comparison of two independent groups (Cannabis User vs. Control). Logistic regression was used to compare baseline group differences in possible clinical cases based on the HADS anxiety and depression cutoff scores (≥8). Additional 2-way ANOVAs were conducted for anxiety and depression scores evaluating interactions between cannabis product use and participant gender, cannabis product use and concomitant use of serotonergic medications, and cannabis product use and psychiatric subtype (Anxiety Only, Depression Only, or Both). As many participants reported use of multiple cannabis product chemotypes, chemotype differences were evaluated using independent-samples t-tests comparing (1) Cannabis Users who did vs. did not use CBD-dominant products and (2) did vs. did not use THC-dominant products. Baseline associations between HADS depression and anxiety scores with past-month average pain on the NPRS were assessed using Pearson correlations.
For longitudinal data, generalized linear mixed effect models were used to evaluate changes over time in HADS subscale scores and the Psychological domain of the WHOQOL-BREF for three groups (1) baseline Controls who initiated cannabis use (“Initiators”; n = 36), (2) baseline Controls who did not initiate cannabis use (“Non-initiators”; n = 23), and (3) baseline Cannabis Users who continued use (“Sustainers”; n = 121). Participants that either discontinued cannabis use (n = 10) or alternated between use and non-use across follow-up assessments (n = 21) were not analyzed due to small sample size and to maintain consistency in analyses, respectively. Generalized linear mixed effect models were used to account for the repeated measurement over time, inclusion of participants with missing data, and inclusion of continuous predictors. Statistical tests evaluated if changes over time differed by group (Group × Time interactions) with within-group tests conducted for significant interactions. Missing data were treated as missing at random and addressed using full-information-maximum-likelihood estimation procedures given evidence that attrition in follow-up was not significantly related to baseline anxiety or depression scores (see Discussion). All tests were conducted as two-tailed tests with an initial alpha level of 0.05. A Bonferroni correction was then used to adjust for multiple comparisons in cross-sectional analyses, setting the new alpha level for these at 0.00132 (0.05/38). Analyses were conducted in R.
Participants were mostly female (79%), Caucasian (83%), and had a mean age of 46 years old (SD = 13) at baseline ( Table 1 ). Participants predominantly reported having comorbid anxiety and depression (51%), followed by anxiety alone (34%), and depression alone (15%). Most participants reported having a co-occurring chronic pain disorder (69%). Just over one-third of participants reported use of serotonergic medication(s) to treat depression and/or anxiety (36%) ( Table 2 details serotonergic medication and doses). Fewer Cannabis Users endorsed serotonergic medication use compared with Controls [OR = 0.49, p < 0.001]. No other differences were observed between groups (all p > 0.17).
|Cannabis Users (n = 368)||Controls (n = 170)||p|
|Age, Mean (SD)||46 (13)||46 (12)||0.96|
|Women, n (%)||286 (78%)||141 (83%)||0.17|
|White, n (%)||298 (85%)||148 (89%)||0.34|
|Post-secondary degree, n (%)||216 (60%)||107 (63%)||0.50|
|Anxiety only, n (%)||134 (36%)||50 (29%)|
|Depression only, n (%)||54 (15%)||27 (16%)|
|Both anxiety and depression, n (%)||180 (49%)||93 (55%)|
|Use of serotonergic medication, n (%)||116 (33%)||80 (51%)|
|Comorbid chronic pain, n (%)||250 (68%)||121 (71%)||0.48|
Percentages calculated for participants without missing data on that item.
Use of serotonergic medication.
|Median daily dose in mg (range; % taking)|
|Cannabis users (n = 116)||Controls (n = 80)|
|Duloxetine||60 (20–120; 21%)||60 (30–120; 19%)|
|Sertraline||100 (25–200; 19%)||100 (12.5–150; 20%)|
|Venlafaxine||150 (37.5–300; 10%)||150 (37.5–300; 21%)|
|Fluoxetine||40 (10–150; 13%)||40 (10–80; 18%)|
|Escitalopram||20 (1.5–20; 16%)||20 (5–30; 14%)|
|Trazodone||100 (37.5–125; 9%)||50 (50–200; 10%)|
|Buspirone||35 (30–60; 7%)||17.5 (5–30; 4%)|
|Mirtazapine||15 (7.5–30; 7%)||22.5 (15–30; 4%)|
|Citalopram||40 (10–60; 5%)||20 (20–40; 4%)|
|Paroxetine||40 (20–40; 3%)||30 (20–40; 3%)|
|Desvenlafaxine||75 (50–150; 3%)||50 (50; 1%)|
|Vortioxetine||10 (10; 2%)||10 (10; 1%)|
|Vilazodone||20 (20; 1%)||–|
|Levomilnacipran||–||– (–, 1%)|
Twenty-nine participants (n = 16 Cannabis Users; n = 13 Controls) reported use of multiple medications.
Cannabis Product Use
Ninety-five participants (26%) endorsed medicinal cannabis use, but did not know the cannabinoid content of the product(s). Among Cannabis Users that did know the chemotype of product(s) they used, most reported use of CBD-dominant products (82%), followed by THC-dominant (23%), balanced THC:CBD (7%), and products for which the highest concentration was a “minor cannabinoid” [e.g., cannabigerol (CBG), cannabinol (CBN); 5%]. Nearly one-third of participants (n = 122) reported use of multiple cannabis product types, including products with unknown chemical composition. These participants were counted as contributing to each of the reported chemotype categories in the distributions and in analyses of medicinal cannabis efficacy by chemotype. For example, participants that indicated concurrent use of both CBD-dominant and THC-dominant products were counted for both the 82 and 23% figures reported above. Most participants that used THC-dominant products also used a CBD-dominant product (83%), but only 24% of participants that used a CBD-dominant product also used a THC-dominant product.
A subset of study participants (n = 139) reported use of specific CBD-dominant products for which certificates of analysis were obtained from manufacturers in order to calculate total daily CBD/THC dose. The mean oral CBD daily dose reported was 61 mg (median = 30 mg; range = 0.4–1,050 mg) and the mean oral THC dose was 2.1 mg (median = 1 mg; range ≤ 0.01–40.3 mg). Mean daily doses were 0.8 mg/kg CBD (median = 0.46 mg/kg; range ≤ 0.01–10.1 mg/kg) and 0.03 mg/kg THC (median = 0.02 mg/kg; range ≤ 0.01–0.39 mg/kg) when adjusted for body weight.
Depression and Anxiety
Cannabis Users reported lower baseline depression [t(528) = 4.995, p < 0.001, and d = 0.47], but not anxiety [t(533) = 1.686, p = 0.09, d = 0.16], on the HADS compared with Controls ( Figure 1 ). Cannabis Users were also more likely to present below the HADS cutoff for clinical concern (scores ≥ 8) for depression [OR = 2.33, p < 0.001], but not anxiety [OR = 1.19, p = 0.50]. These findings remained after correcting for multiple comparisons. No interactions were observed between cannabis use and participant gender, psychiatric subtype, or use of serotonergic medication on anxiety or depression scores (all p > 0.07).
Cannabis Users (n = 368) had reduced depression, but not anxiety, relative to Controls (n = 170) on the HADS at baseline. A greater proportion of Cannabis Users also scored below the HADS cutoff for clinical concern (scores ≥ 8) relative to Controls. Scores ranging from 8 to 10, 11 to 14, and 15 to 21 represent approximate cutoffs for mild, moderate, and severe cases, respectively (83). ***p < 0.001.
Cannabis Users reported significantly better past-month sleep quality than Controls at baseline on the PSQI [t(463) = 3.209, p = 0.001, and d = 0.32]. This remained significant after correction for multiple comparisons.
Quality of Life
Cannabis Users rated their overall quality of life more highly than Controls at baseline [t(525) = −3.327, p < 0.001, and d = 0.31], reported greater health satisfaction [t(525) = −4.248, p < 0.001, and d = 0.40], and had higher Psychological domain scores [t(524) = 5.35, p < 0.001, and d = 0.50] on the WHOQOL-BREF. These findings remained significant after correction for multiple comparisons.
Cannabis Users reported lower past-month average pain at baseline relative to Controls [t(527) = 3.281, p = 0.001, and d = 0.31], but no difference was observed in worst pain on the NPRS [t(525) = 0.987, p = 0.324, and d = 0.09]. Average pain was positively correlated with HADS depression scores in both Cannabis Users [r = 0.4, p < 0.001] and Controls [r = 0.37, p < 0.001], consistent with prior research in people with chronic pain (84). Average past-month pain was also positively correlated with HADS anxiety scores in Cannabis Users, albeit to a lesser extent [r = 0.25, p < 0.001], and uncorrelated in Controls [r = 0.1, p = 0.18]. These findings remained the same after correction for multiple comparisons.
Comparing Cannabis Users based on chemotype indicated that CBD-dominant product use was associated with lower HADS depression scores [t(359) = 2.609, p = 0.009, and d = 0.36], improved quality of life [t(358) = 2.849, p = 0.005, and d = 0.39], and higher Psychological domain scores on the WHOQOL-BREF [t(357) = 2.02, p = 0.04, and d = 0.27] compared to non-use of CBD products. These findings were no longer significant after correction for multiple comparisons. Outcomes did not differ in Cannabis Users based on use vs. non-use of THC dominant products (all p > 0.05; all d < 0.25).
In response to the question “How has therapeutic use of cannabis harmed the participant?,” the majority of Cannabis Users reported no perceived harms (61%) or left this question blank (14%). Harms that were reported included high cost (7%), social stigma or legal issues (5%), intoxication (2%), unpleasant effects associated with inhalation (e.g., smell of smoke, worsening asthma; 2%), impaired cognition (2%), fatigue (2%), and gastrointestinal problems or nausea (1%). Ten participants (3%) reported that medicinal cannabis worsened symptoms of anxiety or caused paranoia, and one participant (< 1%) reported that it worsened symptoms of depression. Five percent of cannabis users reported other unique harms (i.e., for which they represented an n of 1).
The incidence of adverse events differed by chemotype. Though no differences were observed between CBD and non-CBD users, a significantly greater proportion of THC users that responded to this question reported an adverse event relative to non-THC users [38 vs. 26%; p = 0.04]. A higher percentage of THC users reported intoxication [6 vs. 2%; p = 0.04], unpleasant effects associated with inhalation [6 vs. < 1%; p = 0.004], and worsened symptoms of anxiety or paranoia [8 vs. 2%; p = 0.02] relative to non-THC users. A greater proportion of THC users also reported harms involving social stigma or legal issues compared to non-THC users [12 vs. 3%; p = 0.009]. These findings were no longer significant after correction for multiple comparisons.
Longitudinal Impact on Depression and Anxiety
An interaction was observed between timepoint (baseline vs. follow-up) and longitudinal group (Initiator, Sustainer, Non-initiator) for both HADS anxiety [p = 0.04] and depression [p = 0.009] scores, and for Psychological domain scores on the WHOQOL-BREF [p = 0.02]. Within-group analyses indicated that Initiators reported a significant reduction in both mean anxiety [b = −2.52, p < 0.001] and depression [b = −2.57, p < 0.001] scores from baseline to follow-up assessments (i.e., improved symptoms; Figure 2 ); improvement was also observed for Psychological domain scores [b = 1.39, p < 0.001]. This effect was observed to a lesser extent in Sustainers for HADS anxiety [b = −1.40, p < 0.001] and depression [b = −0.65, p = 0.03] and insignificantly in the Psychological domain [b = 0.33, p = 0.07]. Non-initiators did not report changes in HADS anxiety [b = −0.25, p = 0.67], depression [b = −0.67, p = 0.24], or Psychological domain [b = 0.42, p = 0.25] scores during the study.
Participants that either initiated medicinal cannabis use (“Initiators”; n = 36) or continued cannabis use that had been reported at baseline (“Sustainers”; n = 121) reported significantly reduced anxiety and depression on the HADS at follow-up, while participants that did not initiate cannabis use (“Non-initiators”; n = 23) reported no change. Follow-up data presented are collapsed across all completed follow-up assessments for members of each group. *p < 0.05; ***p < 0.001.
Evaluation of clinical cutoffs revealed similar results wherein Initiators showed greater odds of going below clinical cutoffs (scores ≥ 8) (77) at follow-up for HADS anxiety [OR = 14.07, p = 0.002] and depression [OR = 6.47, p = 0.01] scales, Sustainers did to a smaller extent for both anxiety [OR = 3.79, p = 0.001] and depression [OR = 2.56, p = 0.02], but Non-initiators did not show a significant change in odds for either anxiety [OR = 0.03, p = 0.33] or depression [OR = 1.63, p = 0.66].
Despite the high incidence of anxiety and depressive disorders, particularly among women (1), many people suffering with these conditions do not pursue treatment (6, 10–13) and pharmacotherapeutic options remain subpar (14, 23, 25). Here, we evaluated symptoms of anxiety and depression, as well as other general health metrics, in a convenience sample of medicinal Cannabis Users with anxiety and/or depression in comparison with a non-using Control group in a longitudinal web-based survey study. In the cross-sectional comparison at baseline, Cannabis Users self-reported less severe depression, but not anxiety. This effect was strongest among participants using CBD-dominant products, and was not impacted by participant gender or concurrent use of serotonergic antidepressants. Cannabis Users also reported superior sleep, quality of life, and lower average pain relative to Controls at baseline. Adverse effects attributed by participants to cannabis product use were infrequent, were more associated with THC-dominant product use, and, with the exception of nausea, were distinct from those typically associated with antidepressants (21, 23). In longitudinal analyses, participants who initiated medicinal cannabis use during the follow-up period showed a significant reduction in both depression and anxiety symptoms. A similar, albeit smaller magnitude, effect was observed in participants that sustained medicinal cannabis use throughout the study, suggesting an improvement in anxiety and depression symptoms with both the onset of cannabis use and with extended use.
A handful of studies have previously examined the anxiolytic effects of THC (30–32) and CBD (31, 47–49) in clinical populations, and most of these have found a positive effect. While we observed no effect of medicinal cannabis use on anxiety at baseline, participants that initiated cannabis use during the follow-up period reported a significant reduction in anxiety that was not mirrored in Non-initiators. This discrepancy between cross-sectional and longitudinal anxiety outcomes may reflect on the therapeutic window for CBD. As participants may have been using medicinal cannabis for any period of time prior to baseline assessment to be considered a Cannabis User, differences in outcomes may be attributable to the development of tolerance to anxiolytic effects of cannabinoids, although positive effects observed in the Sustainer group suggest otherwise. Alternatively, this discrepancy may reflect a latency period during which the clinical benefits of cannabinoids for anxiety are not yet observed. Controlled clinical studies and dense sampling data (e.g., ecological momentary assessment) are needed to clarify these early-in-treatment effects with greater precision. It is also important to note that the CBD doses used in trials that found an anxiolytic effect were far greater than the average reported by participants in our study, and the time course for anxiolytic efficacy may differ by dose (47–49). Finally, it is possible that anxiolytic effects of CBD may be condition-specific, as symptom improvement has been consistently observed in studies of social anxiety disorder (47–49), but not in obsessive compulsive disorder (31). The heterogeneity of our sample and reliance on self-report for psychiatric condition(s) of a given participant may have precluded observation of anxiolysis at baseline.
Assessment of the antidepressant effects of medicinal cannabis use has thus far been more limited. In our study, we found that Cannabis Users reported reduced depression relative to non-using Controls at baseline. Consistent with prior research in people with comorbid chronic pain (43–45), we found that use of THC-dominant products was not superior to use of non-THC-dominant products in alleviating depression symptoms. In contrast, participants that reported use of CBD-dominant products provided significantly lower depression scores relative to those that did not, consistent with preclinical findings (57, 85, 86). Cannabis Users also reported superior sleep, average pain, and quality of life relative to Controls. This is unsurprising given the interrelated nature of these constructs with depression (87–89), and both pain and quality of life have been shown to be improved with traditional antidepressant treatment (90, 91). Consistent with baseline outcomes, we found that initiation of medicinal cannabis use was associated with a significant reduction in depressive symptoms, sustained use was associated with a modest reduction, and participants that did not use cannabis at all showed no difference in symptom expression between baseline and follow-up. These combined cross-sectional and longitudinal findings show a consistent antidepressant effect of medicinal cannabis.
This study has several limitations. Notably, these outcomes rely entirely on participant self-report. It is possible that some of the symptom improvement reported by medicinal Cannabis Users can be attributable to an expectancy effect, especially in consideration of the low daily CBD doses reported by participants relative to those used in previous clinical studies (31, 47–49). However, as research in this area is still in its infancy, it is presently unknown what constitutes an optimal dose to maximize antidepressant/anxiolytic efficacy and minimize incidence of side effects, particularly when dosing over an extended period. It is also unclear if minor cannabinoids or terpenes present in whole-plant or “full spectrum” products used in this study, compared with isolated pure chemical substances used in previous research, confer additional therapeutic benefits via an entourage effect (92). Similarly, Controls were people that were considering the use of medicinal cannabis to treat their condition. Therefore, it is also not surprising that people who believed medicinal cannabis might assist with their condition enough to initiate use would perceive a substantial benefit. This study additionally represents a convenience sample of people registered with the Realm of Caring foundation willing to complete lengthy online assessments for only modest incentives. People with mild symptoms, with more responsibilities in daily life, or who did not see a substantial improvement from medicinal cannabis treatment may have been less likely to complete the survey. Finally, dosing data could only be obtained for about half of the medicinal Cannabis Users given poor or non-existent labeling information on some retail and all black market cannabis products, and most participants did not complete a follow-up assessment. Supplemental analyses showed no significant differences in baseline health behavior between participants who did and did not provide follow-up data, p > 0.39, d < 0.08.
In sum, this study suggests that use of CBD-dominant cannabis products is associated with reduced depression in a sample of mostly female, Caucasian adults. The study extends prior research by including a control group, and through a study design that includes both cross-sectional and within-subject, longitudinal comparisons. Though antidepressant effects of CBD have been consistently reported preclinically (57, 85, 86), our work contributes to the literature by showing a potential for translation across species without many of the negative side effects associated with traditional antidepressants (21, 23). It is recommended that this antidepressant effect of CBD be evaluated further in placebo-controlled clinical trials, and that participants remain under observation following treatment completion to confirm the absence of a discontinuation syndrome. Additionally, considering the average daily CBD dose reported in our study was quite low relative to previous clinical work (31, 47–49), future research is necessary to determine best dosing practices to achieve optimal antidepressant effects. Medicinal cannabis products may also alleviate anxiety, but it is unclear if this effect is gated by duration of use. Placebo-controlled clinical trials are necessary to further explore the potential efficacy of CBD in the treatment of anxiety and depression.
Data Availability Statement
The datasets presented in this article are not readily available because the corresponding author does not own this data. Requests to access the datasets should be directed to Ryan Vandrey ([email protected]).
The studies involving human participants were reviewed and approved by Institutional Review Board of Johns Hopkins University. The patients/participants provided their written informed consent to participate in this study.
HJ, RV, MB-M, NS, and JM conceptualized and executed the parent survey. EM conceptualized this secondary analysis, curated the data, and drafted the original outline. EM and JS conducted statistical analyses and created the figures and tables. EM, JS, and RV wrote the first and final manuscript drafts. All authors reviewed and edited both manuscript drafts and approved the final manuscript.
This work was supported by the Realm of Caring Foundation and by National Institute on Drug Abuse (NIDA) grants T32-DA007288 (EM) and T32-DA007209 (NS and JS).
Conflict of Interest
RV has received financial compensation as a consultant or advisory board member from Canopy Growth Corporation, MyMD Pharmaceuticals, and Syqe Medical Ltd. MB-M is an employee of Canopy Growth Corporation and past board of directors member for AusCann Group Holdings Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
The authors would like to thank the study participants and staff at the Realm of Caring Foundation and Johns Hopkins University School of Medicine that assisted with this project.
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