By Cannabis Training University (Own work) [CC BY-SA 3.0]
Source: By Cannabis Training University (Own work) [CC BY-SA 3.0]

In the last two posts I discussed cannabis from the perspectives of its underlying characteristics as a pharmacological agent and its psychological impact on the mind. Now we are ready to turn to the issue of whether it can be an effective treatment for insomnia.

Insomnia is the most common sleep disorder and its chronic type affects over 10% of the population at any given time. It is characterized by subjective difficulty falling or staying asleep with frequent and prolonged middle of the night awakenings and/or early morning awakenings, and nonrestorative sleep that results in daytime symptoms such as low mood, irritability, difficulty focusing, and memory problems that significantly affect daytime functioning.

At this time, the effective treatments for insomnia are cognitive behavioral therapy (CBT) and certain medications that work on a number of different neurotransmitter systems. While CBT is effective for about 70% - 80% of patients, it does require a significant amount of work. It can result in long term gains in improved quality and quantity of sleep. Sleeping medications are really best for short term use but many patients develop a type of dependency on them and come to believe they will be unable to sleep without medication. It can be very frightening and difficult to break this dependency. The primary reason for this is that suddenly stopping sleeping medication after prolonged use results in intense rebound insomnia that is as bad or worse than the original insomnia that the medication was taken to treat. For some of the older sleeping medications, this can continue for an agonizingly long time and people will often just give up and go back to using the medication. Some of the newer medications tend to have a shorter period of rebound, but it can still be very difficult to tolerate. Usually a slow taper combined with a shift to cognitive behavioral strategies works best to successfully shift away from sleep medication as this minimizes the intensity of any rebound.

The nature of the health care or, perhaps more accurately, the illness management, system in the US tends to press for quick solutions that can be prescribed in a brief interaction with a primary care physician. Obviously this will make treatment with medication a much more likely outcome than a referral for CBT. Some patients do not want to take powerful pharmaceutical or over the counter sleeping medications and may not have access to treatment with cognitive behavioral therapy. The question is: is cannabis a reasonable alternative in this situation?

Increasing numbers of patients are already using cannabis for treatment of their insomnia or for another medical or psychological disorder that has insomnia as a symptom of it. They are doing this either through the traditional illicit market or as a part of the newer legal (under state law) medical marijuana programs. As we go forward, and if more states, or even the federal government, end prohibition of the use of cannabis, it is likely that more people will be using it to manage their insomnia.

What are the characteristics of an effective treatment for insomnia? We would have to include efficacy, effectiveness, feasibility, safety, ease of use, side effects, and cost. How does cannabis measure up in each of these domains?

Efficacy in medicine refers to the demonstrated ability of a treatment to bring about beneficial effects. This is what is measured in controlled trials of a medication and is likely to produce better results than what will be experienced in the field because of the careful selection of patients for the study and rigorous adherence to the method of using it. Obviously this research is expensive to conduct.  Currently only MAPS is doing these types of studies and then only regarding treatment of PTSD.

The efficacy of cannabis is thus as yet undetermined. Early studies indicated that CBD could indeed promote sleep in insomnia patients (Carlini & Cunha, 1981). Some recent research has supported that cannabis can shorten the time it takes to fall asleep and make it easier to fall asleep (Gorelick et al., 2013) and may have other effects such as deepening sleep. There is other evidence that chronic use of cannabis actually down regulates the endocannabinoid system and thus may negatively impact on sleep quality over time (Maple, McDaniel, Shollenbarger, & Lisdahl, 2016). Some research has indicated that chronic use of marijuana worsens insomnia, while less frequent use does not. There could be a number of reasons for this. One is that people who are using marijuana chronically have more anxiety or other psychological problems and this is what is actually negatively affecting their sleep. It could also be that chronic administration of cannabis has a similar dependency inducing effect as does other sleeping medication. Clearly, much more research is needed with regard to efficacy.

Effectiveness refers to how a medication actually works in day to day situations out of the laboratory. Since efficacy has yet to be definitively determined, it is difficult to assess effectiveness and we are left relying on the anecdotal evidence presented by patients. From the reports I have received, I would say that some patients believe that they get significant benefit while others do not. There are so many variables involved that it is hard to know exactly what this means. It could be that certain patients have an endocannabinoid system that benefits from cannabis augmentation while others do not. It could also be that we have not fully worked out the proper strains, dosages, ratios of THC to CBD, or the most effective route of administration.

Feasibility is the practicality of a project. This is relatively straightforward. Cannabis can and is being used by many patients for a number of psychological and medical conditions. This was widespread even under conditions of extreme illegality and is even more so now that there is greater acceptance of medical marijuana and easing of some legal restrictions. Not only is it easy to supply this plant, it can even be grown at home for personal consumption. The major requirement is to provide adequate information and education on use so that patients can best protect their health.

Safety is a concern with any medication. Cannabis has no known lethal dose in humans and is generally considered to be relatively benign with regard to its physical effects. Psychologically it can be very challenging due to the anxiety, panic, and paranoia that it can cause. Recovery from this is typically rapid. The primary concern is any unknown long term negative effect on the body and the potential for cannabis to increase the risk for developing serious mental disorders such as psychosis. Mixing cannabis with other drugs is frequently done but is clearly not recommended.  Anecdotal evidence regarding interactions with other drugs is available. For example, mixing cannabis with alcohol often increases the effect of both drugs. Research has shown that combining alcohol with cannabis raises blood levels of THC (Hartman, et al., 2015). This would indeed potentiate the effects of the cannabis. It is also known that CBD affects the liver system involved in the metabolism of many drugs (Bornheim & Grillo, 1998) and this could affect the levels of other medications being taken.  When used as a medication, cannabis would have to be taken with the recognition that it can cause psychological difficulties in susceptible people and it should not be mixed with other psychoactive medications. While CBD appears to be safe further research is needed regarding the effect of cannabis on the metabolizing of other drugs (Bergamaschi et al., 2011).

Safety concerns have also been raised by the increased potency of cannabis products and the potential for contamination (McLaren, et al., 2008). To date there has been relatively little evidence of problems in this regard. It is likely that as cannabis preparations grow stronger, patients simple titrate down the dose consumed.  For example, when smoking a stronger than typically used product, a patient may take a less deep inhalation so as to lessen the intensity of the stronger product’s effect. Edibles present a problem in this regard as it is possible to take an overly large dose and have no indication of this for up to several hours. With regard to contamination, there has been relatively little official effort to monitor this. To date, there appear to be few if any reports of difficulties related to contamination. Concerns have recently been raised about bacterial and mold contaminants in medical marijuana, as this could be a risk for ill patients, especially when consumed by smoking or vaporizing. If medical marijuana is to attain acceptance as a safe treatment, it will be necessary for the industry to find ways of assuring that the product is free of any contaminants.  

Ease of use is a concern with any treatment. In the sleep field a primary example of the problems that can occur when a treatment is difficult to use is CPAP therapy for sleep apnea. While CPAP is an accepted and effective treatment for sleep apnea, is it often difficult for patients to acclimate to and use the equipment on a regular basis. As a result, using CPAP as an effective treatment may not be viable for certain patients. The viability of medical cannabis as a treatment has expanded significantly in recent years. Historically most marijuana was consumed by smoking with the attendant problems of respiratory irritation, exposure to potentially dangerous combustion products, and the odor that non-users might object to (or use to track down and stop the use). Now cannabis and concentrates can be consumed by vaporization and it can also be eaten in foods or drinks. Consumption of medical cannabis has  come very close to being as easy as taking a  sleeping pill.

Most sleep aides are pills or liquids, such as Ambien or Benadryl. Historically, smoking has been used as the delivery mechanism for cannabis. It is effective as it converts THCA into THC, but it also exposes the user to the potentially lung damaging effects of smoke. As cannabis has moved from the illicit market to the legitimate market, efforts have been made, some of which started many years ago, to improve the experience and safety of consumption. These include the use of water pipes, concentrates, edibles, and vaporization. Water pipes have been used for many years but may be of limited effectiveness in terms of eliminating the harmful components of cannabis smoke. Vaporization as an alternative has been growing in popularity and studies by MAPS showed that THC was liberated from cannabis plant matter at a temperature of 200 degrees Celsius without burning the material. This method essentially eliminated the known toxins in marijuana smoke such as benzene, toluene, and naphthalene. Concentrates such as wax derived from the plant material may also be vaporized to give a large dose of THC from a small amount of material. THC is also being extracted from cannabis and used as an ingredient in candies, cookies, and soft drinks. Some of these methods may be more acceptable to certain patients than others.

The side effects of a medication are often a major consideration in whether or not to use it. If the side effects outweigh the benefits, a patient is unlikely to continue using the medication. This is, I think, a major concern for many insomnia patients who may consider cannabis for insomnia. In fact, early consideration of its use as a sleep inducing medication was limited because of the hallucinogenic effects, which might not be well tolerated by patients (Carlini & Cunha, 1981). Medical marijuana patients have been dealing with this issue since the first modern widespread use of cannabis for legal medical purposes started in California after the passage of the medical marijuana law in 1996. Some patients like the psychoactive effects of cannabis and do not consider this a negative side effect. Others seem to develop a tolerance to these effects over time so that they are not of concern. Still other patients do not like them and have gravitated toward strains and extracts of cannabis that favor CBD over THC. It is likely that for some set of patients this will be a deal breaker for use of cannabis for insomnia, while for others it will not.

To further elaborate on this issue, the psychological effects of THC are going to vary depending on the amount and rapidity with which it is ingested and on the particular cell populations in any given individual. As with all psychoactive drugs, this will also be influenced by the set and setting. An individual’s belief system will, at least in part, determine how effects of a drug are experienced. Someone who is familiar with how THC affects them and expects these effects to be meaningful or pleasant will tend to experience even very strong effects as positive and interesting. Someone who is fearful or anxious about how the drug will affect them may have a more frightening experience even if subjectively both are experiencing similar drug effects. Likewise, the setting will be very important. If the environment is positive and supportive it is more likely that the drug effects will be interpreted positively while if it is one that is non supportive it will bias the perception of the experience in a negative direction. This is not unlike the difference between bungee diving and falling off the same cliff. In the first case, the mind will react with a flight or fight response but it will be interpreted as, yes, frightening, but also as interesting and exciting. After all, cognitively the person is aware of the bungee cord and the very strong likelihood that they will not actually hit the bottom of the cliff. Falling off the cliff without the bungee cord, on the other hand, will most likely only produce fear and panic because there is no mediating cognitive process indicating safety. Understandable labeling, adequate instruction in proper use, and starting out at a low dose and working up are strategies that can help significant reduce the possible negative psychological side effects of using cannabis.

Cost is a significant consideration in the implementation of a new therapeutic approach. For example, there has been considerable debate over the cost effectiveness of many new medications that have been introduced that have little, if any, benefits over existing medications but which may expose users to greater and unknown risks such as unacceptable side effects. I am not in a position to do a careful economic analysis of the cost effectiveness of cannabis as a sleep aide. It is clear, however, that with legalization the cost of cannabis is dropping significantly and most states have provided for home growing, which could, over time, dramatically lower costs for patients willing to take on the sometimes daunting task of growing this plant at home. Most patients that I work with, who report finding cannabis effective, find the cost somewhat high but acceptable as they use a very small quantity to get to sleep. If restrictions on the cannabis industry imposed by federal law are eased or ended, it could dramatically decrease the cost of medical cannabis. For example, growing cannabis in green houses or in fields would greatly decrease the costs of indoor growing under artificial light. For another, being able to deduct business expenses, which is accepted practice in other industries, would further reduce cost. Given that cannabis is a hardy plant that grows profusely all around the planet, it seems that cost could be reduced to an acceptable level.

With all of the new information related to cannabis, it still remains unclear if it can be an effective treatment for insomnia. Clearly, there is anecdotal and research evidence that, for at least occasional use, it can be beneficial for sleep. Chronic use is less clear and may have a negative impact, as is the case with other sleeping medications. On most of the parameters discussed, it seems feasible to develop an acceptable regimen for effective use. Quality control in production and public education will be crucial. The major road block to further progress is the great difficulty in doing research on the beneficial effects of cannabis because of its legal status as a schedule 1 drug, which assumes no accepted medical use and a high potential for abuse. In the report of bacteria and mold found in medical marijuana, the analysis could not be done at the university but had to be conducted at a private laboratory as cannabis cannot be kept at universities receiving federal funding of any kind. Despite strict, government controlled access to marijuana for use in medical research, will researchers continue to persist in pursuing this hard-to-get substance for marijuana-based medical projects such as it use in the treatment of insomnia?  Only time will tell.

References:

Bergamaschi M.M., Queiroz, R.H.C., Crippa, J.A.S., & Zuardi, A.W. (2011). Current Drug Safety, 6 (4), 1 – 13.

Bornheim, L.M. & Grillo, M.P. (1998). Characterization of Cytochrome P450 3A Inactivation by Cannabidiol: Possible Involvement of Cannabidiol-Hydroxyquinone as a P450 Inactivator.  Chem. Res. Toxicol. 1998, 11, 1209-1216.

Carlini, E.A. & Cunha, J.M. (1981). Hypnotic and Antiepileptic Effects of Cannabidiol. Journal Clin Pharmacol, 1981 Aug-Sep; 21(8-9 Suppl), 417S-427S. doi: 10.1002/j.1552-4604.1981.tb02622.x

Gorelick, D.A., Goodwin, R.S., Schwilke, E., Schroeder, J.R., Schwope, D.M., Kelly, D.L., Ortemann-Renon, C., Bonnet, D., & Huestis, M.A. (2013). Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers. The American Journal on Addictions, 22 (5), 510 – 514. DOI: 10.1111/j.1521-0391.2013.12003.x

Hartman, R.L., Brown, T.L., Milzvetz, G., Spurgin, A., Gorelick, D.A, Gaffney, G., & Huestis, M.A. (2015). Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. Clinical Chemistry 61 (6), 850 – 869, doi:10.1373/clinchem.2015.238287.

Maple, K.E., McDaniel, K.A., Shollenbarger, S.G. & Lisdahl, K.M. (2016). Dose-dependent cannabis use, depressive symptoms, and FAAH genotype predict sleep quality in emerging adults: a pilot study. The American Journal of Drug and Alcohol Abuse, 42 (4), 431-440.

McLaren, J., Swift, W., Dillon, P., & Allsop, S. (2008). Cannabis potency and contamination: A review of the literature. Addiction, 103, 1100–1109. doi:10.1111/j.1360-0443.2008.02230.x

"Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.. Licensed under Public Domain via Wikimedia Commons a/File:Yin_and_Yang.svg
Source: "Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.. Licensed under Public Domain via Wikimedia Commons a/File:Yin_and_Yang.svg

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