CATR: Can you define cannabis withdrawal and tell us about its symptoms?

Dr. Budney: Cannabis withdrawal starts 24–48 hours after somebody stops cannabis. The symptoms can vary, but there is a “core” of common symptoms that are shared between withdrawal syndromes from other substances—irritability, sleep issues, mood issues, and appetite changes. Specific to cannabis withdrawal, people tend to lose their appetite. Some report strange dreams, though I think many of those cases are probably people starting to dream again. Cannabis tends to suppress dreaming. Physical symptoms include nausea, headaches, and hot flashes, which are usually fairly mild. On occasion, people will have more severe symptoms. When that happens, they usually involve nausea or stomach distress. 

CATR: Is withdrawal severity dose-dependent? 

Dr. Budney: We don’t really know. Studies tend to have sample sizes of only a few dozen participants, so differentiating withdrawal severity between them is hard, especially because participants tend to be a uniform population of people who use fairly heavily. One would expect a dose-dependent effect physiologically, but it’s not that clean-cut. In fact, it is not so clear with tobacco, opiates, or any other substance either. Anecdotally, we see huge individual differences that would be difficult to accurately predict. Plenty of people who use large amounts of cannabis have little or no withdrawal, while others who use a moderate amount may have fairly severe ­symptoms. 

CATR: How long does cannabis withdrawal last?

Dr. Budney: At least in lab studies, most people start to feel better within a week, and symptoms are gone after two weeks. The symptom that lingers the longest is sleep issues. In our studies, we’ve followed people over a month and sleep never quite returned to baseline (Budney AJ et al, J Abnorm Psychol 2003;112:393–402).

CATR: THC is lipophilic, so it’s stored in the body for a long time. Do you think THC’s lipophilicity has anything to do with the time course of withdrawal?

Dr. Budney: I don’t think it has great influence. THC may be detectable for a long time, but what matters are the physiological and behavioral effects of the drug—for THC, those last for a few hours. I referred to “core” withdrawal symptoms earlier, which are symptoms that occur in most, if not all, of the substance withdrawal syndromes. Even when drugs have very different mechanisms of action, these core withdrawal symptoms are shared. That’s because withdrawal syndromes have as much to do with the brain’s reward system as the effects of the drugs themselves. It’s not about an opioid receptor versus a cannabinoid receptor—it’s a withdrawal from reward. When you take a regularly recurring, potent reinforcer away, many patients experience irritability, depression, and disturbed sleep. There are a few drug-specific symptoms that have to do with how the drug functions in the body: pain and achiness in opioid withdrawal, seizures and tremor in alcohol withdrawal. But otherwise, most withdrawal symptoms are common across drugs.

CATR: Do these withdrawal symptoms interfere with someone’s ability to cut back or stop using?

Dr. Budney: Most certainly. Think about it logically: If you’re miserable and you know smoking a joint will take the misery away, that’s going to make you more likely to smoke. And to my earlier point about core symptoms, patients report that withdrawal challenges their ability to stay sober from all substances, not just cannabis. We’ve done outpatient studies of cannabis withdrawal in which we keep in touch with the participant’s significant other. Several times a participant’s partner contacted us and pleaded, “Please let him go back to smoking. He’s driving me crazy. He’s so much more likable when he’s smoking.” Again, this doesn’t happen to everybody, but the withdrawal is a big challenge for some. 

CATR: How do you discuss withdrawal with patients? I imagine some haven’t heard of it.

Dr. Budney: Most have experienced it themselves by the time they get to treatment. For those who are unfamiliar, we explain the symptoms, let them know what they may experience, and reassure them it’s normal and will go away if they can abstain long enough. I’ve never had anyone who was shocked to learn about cannabis withdrawal. I think pretty much everyone is familiar with the fact that quitting tobacco smoking can be difficult, largely because of withdrawal symptoms. So I sometimes draw parallels there, pointing out the opposite appetite effects. In fact, we’ve compared cannabis and tobacco withdrawal in the laboratory and found that the discomfort and the irritability are about the same. About half of people have more withdrawal from tobacco and about half have more withdrawal from cannabis (Budney AJ et al, Subst Abuse Treat 2008;35:362–368).

CATR: Does the similar withdrawal severity from tobacco and cannabis translate into the two being equally difficult to quit?

Dr. Budney: For people in our study who used both, tobacco came out as a little harder to quit than cannabis. However, participants tended to have smoked tobacco for a longer duration and more frequently than cannabis. It’s common to smoke one pack of cigarettes per day—that’s 20 times per day. People rarely smoke cannabis 20 times a day.

CATR: The development of easy-to-use and easy-to-conceal vaping devices must lead to higher THC consumption.

Dr. Budney: That’s probably correct. It likely translates into worsening withdrawal syndromes overall, but there aren’t many recent clinical trials being done with cannabis users looking to quit. However, we know that the amount of THC people are taking in is quite high. We are investigating how much THC people are consuming in the “real world” by recruiting participants via social media. These are mostly daily users, and they are taking in much more THC than we anticipated. Consequently, there appears to be a lot of tolerance because many seem to be functioning fairly well, at least by their self-reports.

CATR: How much THC are we talking about?

Dr. Budney: A conservative estimate of the mean amount of THC consumed daily by participants in our first study, which included over 3,200 daily cannabis users, was between 92 mg and 269 mg a day (Budney A et al, Cannabis Cannabinoid Res 2024;9(2):688–698). Another study we did found that 25% of participants reported 285 mg per day and 13% reported over 500 mg per day (Borodovsky JT et al, Addiction 2024; Epub ahead of print). 

CATR: Can you put these amounts into perspective?

Dr. Budney: Non-cannabis users will feel high from just 10 mg of THC, and most regular heavy users feel high at 20–30 mg. Most cannabis gummies are sold in 5 mg or 10 mg pieces. Smoking an entire 20% THC joint—the most common potency sold in dispensaries—delivers approximately 60 mg of THC. So, many people are taking in very large amounts of THC. This leads to the question of tolerance, something that has not been investigated thoroughly for cannabis. We have always known that tolerance develops, but now that people have easy access to high-potency cannabis products, it is becoming increasingly important to understand how much tolerance develops and how that affects behavior and cognition. We know that tolerance is a huge issue with opioids, of course, as it is for many substances. And returning to the topic of withdrawal, you would expect people who have developed substantial tolerance to be vulnerable to more severe withdrawal symptoms when stopping. 

CATR: That’s a big challenge in the cannabis literature: The cannabis being used in clinical trials is not the same as what people are using in the community.

Dr. Budney: That’s true. In our studies that I referred to, we had many people reporting that they use 200–1000 mg of THC a day, but only a few cannabis self-administration studies have delivered over 120 mg (Schlienz NJ et al, Drug Alcohol Depend 2018;187:254–260). The cannabis provided to participants in research studies is generally much weaker than what is available at your local corner dispensary. I believe that the National Institute on Drug Abuse now can provide cannabis that is 9% THC, whereas the average potency of cannabis flower sold in shops is 20%, with concentrate products approaching 90% THC.

CATR: That must affect the generalizability of study results.

Dr. Budney: I’m sure it does to some extent. But even with research cannabis (6%–9% potency), participants report getting high. They report liking it. And until recently, in the alcohol literature, no one really studied blood alcohol levels (BAL) much over 0.100. We don’t have studies with BAL over 0.20, which we commonly observe in practice. 

CATR: You mentioned that withdrawal from cannabis can be variable. How common is it? 

Dr. Budney: For daily cannabis users, I’d estimate 40%–70% will experience some degree of withdrawal, with lower estimates for those using less often (Bahji A et al, JAMA Netw Open 2020;3(4):e202370). And what about those consuming very high amounts of THC or using high-concentration THC products? We’re not quite sure at this point how that translates into prevalence of withdrawal, but again, the assumption is that it likely increases the probability and severity of withdrawal experiences.

CATR: Is there a way to predict who is more likely to experience withdrawal?

Dr. Budney: It’s similar to other substances. The more someone uses, the more likely they are to experience withdrawal. But there is going to be variability—you can predict risk to some degree, but accuracy is not going to be great. In my experience, the best way to predict is to ask the consumer. What happened the last time they stopped smoking? Did they have withdrawal symptoms? If they did, then they are likely to have them again.

CATR: What can we do for patients who experience cannabis withdrawal as a significant barrier to abstinence?

Dr. Budney: First, there is reassurance: Let them know withdrawal symptoms are expected, are normal, and don’t last forever. Beyond that, general wellness advice can go a long way: Get exercise, drink plenty of water, and practice good sleep hygiene.

CATR: Are there specific treatments?

Dr. Budney: Most recently, researchers have been investigating novel agents specific to the cannabinoid signaling pathway, but there is nothing ready for clinical use (Haney M et al, Nat Med 2023;29(6):1487–1499). The most typical approaches are reassurance and basic behavioral strategies to treat symptoms. However, multiple medication approaches have been investigated with some promising results (Connor JP et al, Addiction 2022;117(7):2075–2095). Many consumers use cannabis as a sleep aid, so insomnia can be a real issue during withdrawal. These patients can benefit from a mild sleep medication to help get them over the hump. Irritability and anxiety might be treated with alpha-2 agonists like guanfacine. Depressed mood and anxiety can be treated with selective serotonin reuptake inhibitors. Turning to GI issues, some patients get so nauseous that they have trouble eating. For these patients, we’ve found prochlorperazine can be helpful. After all, if you can’t eat, you’re not going to tolerate withdrawal for very long. 

CATR: What about just giving the patient THC?

Dr. Budney: These days, many people have access to cannabis from dispensaries, though I wouldn’t recommend going that route if someone is highly motivated to abstain. Constructing a careful taper schedule out of dispensary products is going to be challenging. Pharmaceutical cannabis formulations are available—nabiximols (Sativex), a mouth spray that contains THC and CBD, and dronabinol (Marinol) are examples. There has been interest and some research on this approach (Allsop DJ et al, Clin Pharmacol Ther 2015;97(6):571–574). 

CATR: Why hasn’t this approach become standard?

Dr. Budney: It’s probably used outside of standard treatment settings all the time. But we must ask: What are the therapeutic goals? The goal shouldn’t be just to relieve withdrawal. Most consumers are aiming for abstinence or substantial reduction in use. Sure, giving someone THC will help relieve withdrawal symptoms temporarily, but there is no indication that this will help them one or two months down the line. I’ve wondered to myself why so many people struggle to quit cannabis, since in many ways, cannabis use disorder is relatively less severe than most other substance use disorders. I think the answer lies with the fact that, just like other drugs or cigarettes, cannabis becomes ingrained in a person’s lifestyle. We sometimes focus on withdrawal as the target. Withdrawal should be a target along the path to change, but treating withdrawal has never been the answer for those seeking substantial change. We can get most people through withdrawal syndromes relatively easily; the key is what they do on the other side. It’s an important first step, but that’s just what it is—a first step. We need to make sure that our patients understand this from the outset.

CATR: Thank you for your time, Dr. Budney.