Treatment of Insomnia: Cannabis Reconsidered, Part Three
Cannabis has complex effects that may complicate its use as insomnia treatment.
Posted June 30, 2017
Patients who may be considering or are using cannabis as a treatment for insomnia need information about how this drug affects the nervous system and what kinds of effects they may experience psychologically. The effects of cannabis are complex because of the unique pharmacology of its constituent components and how it interacts with the mind and body.
As discussed in the previous post, two major active drugs have been discovered in cannabis: THC and CBD. These chemicals are similar to the signaling molecules naturally found in the endocannabinoid system of mammals including humans. This system consists of the endocannabinoid signaling chemicals and the specialized receptors that detect and react to them. This system is extensively distributed throughout the nervous and immune systems and is involved in the regulation of numerous physiological and homeostatic processes, some of which have psychological ramifications. This system works by allowing cells further down in the chain of processing to let upstream cells know how to modulate the input they are passing downstream.
These chemical messengers are involved in the regulation of functions such as pain perception, mood, memory, sleep and food seeking. For example, the endocannabinoid system is involved in the memory process of forgetting. Forgetting is actually very important. Think of how hard it would be to find your car if you could remember perfectly every single place you had ever parked. The same would apply if you remembered vividly every previous interaction with a person rather than giving salience to more recent interactions. Trying to wade through that volume of information would be taxing and could produce errors. Keeping memory to a reasonable size involves getting rid of useless, redundant, or out of date information. In the case of traumatic events, an inability to forget or reduce the salience of a long ago event or person interferes with present day optimal functioning, as in PTSD.
THC and CBD, found in products of the cannabis plant, interact with the endocannabinoid receptors because of their similarity to the endocannabinoids already present in the nervous system. This makes sense when considering the well-known effects of smoking marijuana. Pain is relieved, mood (usually) lifts, short term memory problems occur, relaxation and sleepiness may be experienced, and, well, the “munchies” can happen. If these effects can be brought to bear on clinical illness, patients could experience significant benefits such as, relief from pain, improvement in depression, changes in memories of traumatic experiences, the return of appetite after chemotherapy for cancer, and help in falling asleep for those with insomnia.
The known cannabinoid receptors are designated as CB1 and CB2. CB1 is primarily located in the nervous system and is activated by the endocannabinoid anandamide and by the exogenous cannabinoid, THC. CB2 is found primarily in the immune system and is activated by the endocannabinoid 2-AG and the exogenous cannabinoid, CBD.
CBD is non-psychoactive and has anti-inflammatory, anti-anxiety, and immune system enhancing effects (Gallily, Yekhtin, & Hanuš, 2015). This is why it may be beneficial for reducing pain or controlling inflammatory illnesses. There is evidence that CBD modifies the effects of THC (Bhattacharyya et al., 2010). Currently, CBD is more available in the US than THC and may be better tolerated by patients because its lack of psychoactive effects. The medical marijuana industry is aware of these qualities and efforts have made to develop strains of cannabis or concentrates that have a favorable ratio of THC to CBD or products that only contain CBD. Oils containing CBD without THC are available and may be purchased at some establishments specializing in nutraceutical supplements, although this is questionable legally under federal law and in terms of safety at this time. It may be helpful in treating disorders such as epilepsy and Crohn’s disease.
Because of its psychoactive effects, THC is being researched for use as a psychotherapeutic agent. It too may have many of the positive medicinal qualities ascribed to CBD but with the potential challenge to patients of being psychoactive.
Psychoactive drugs typically are classed into the categories of tranquilizers (meaning here, antipsychotics or what were referred to in the past as “major tranquilizers”), depressants, stimulants and hallucinogens (Kim, 2012). THC is usually considered to have hallucinogenic, depressant, and stimulant characteristics (Kim, 2012). In cannabis, when THC is balanced with CBD, it may have additional tranquilizing effects. (For other graphical representation of the relationship between the four types of psychoactive substances see Figure 2, p 2, in Kim, 2012; and Schwartz’s updated version of the Venn diagram shown above.)
The psychoactive effects that THC has are mediated by the nature of the endocannabinoid system of the individual using it and by the dose and route of absorption. Some people tend to have a particular reaction to THC and this may vary considerably from one person to another. Some individuals, for example, will become anxious and excited from even a small amount of THC, while others might become relaxed and drowsy. While, in general, smaller doses are associated with excitation, higher doses with sedation, and very high doses with hallucinogenic and psychotomimetic effects (Stahl, 2013), it has been extremely difficult to establish a dose response relationship for cannabis and its effects (Ramesh, Haney, & Cooper, 2013).
Cannabis, because of the entourage effect, potentially has a tranquillizing effect as noted above. This appears to be because CBD modifies the effect of THC to reduce its hallucinogenic properties and to enhance its more relaxing and depressant effects (Bhattacharyya et al., 2010). The ratio of these two substances in any sample of cannabis will therefore have an effect on its psychological effects. A cannabis product with relatively high levels of CBD would be most likely to be beneficial to a patient seeking help with insomnia.
There are two or three generally recognized species of cannabis plant – sativa, indica, and possibly ruderalis (Craker, L. E. & Gardner, Z., 2010). Ruderalis is not universally recognized as a separate species. Historically, sativa was associated with low THC content and high fiber content and was used in Europe for hemp, while indica was associated with high THC content and used as a drug. The current situation is not as clear because of selective breeding, often driven by the economic demands of the illicit market to increase THC content so as to reduce the volume of materials needed to be smuggled and to provide a potent product that consumers would be willing to pay for - which has resulted in very high THC content in sativa products. In the current medical marijuana market there are balanced THC/CBD hybrid indica/sativa products for medicinal use, high THC/low CBD sativa products that are more “energizing” and can be used during the day and high CBD/lower THC indica products for use later in the day or the help with sleep.
When substances, including drugs, are orally ingested, they are first metabolized in the liver in what is known as first pass metabolism before they interact with other systems of the body. This allows for the rapid detoxification of chemicals that could be harmful if allowed to pass unchanged into the body. In the case of THC this metabolic change results in an active metabolite, 11-OH-THC, that has equal or greater psychoactive properties than THC itself and is more easily absorbed through the blood brain barrier (Huestis, 2007). The slower absorption into circulation of THC when ingested as opposed to inhaled, the differences in peak concentrations obtained by the two different routes, and the effects of active metabolites, help account for the often reported differences in oral and inhaled consumption of marijuana.
When inhaled the effects appear rapidly, last several hours, and gradually fall off. In the case of oral consumption, the effects take considerably longer to appear and may be significantly stronger and longer lasting. Because many patients do not want to smoke and risk exposure to harmful chemical byproducts of combustion, edible forms of cannabis have become very popular. Several years ago Maureen Dowd, a columnist for the New York Times, went to Colorado to do some field research on the legal marijuana scene, ate too large a portion of a cannabis infused candy bar, and ended up on her hotel bed “curled up in a hallucinatory state for the next eight hours.” Fortunately for her, cannabis has no known lethal dose, and unlike alcohol, where an overdose could mean a trip to the hospital or morgue, she was able to be back at her desk writing the report of her experience the next day. (To be fair, she does note a number of sensational reports of people acting in very dangerous ways after over consumption of cannabis edibles. Proper labeling of cannabis products and adequate education of consumers are clearly important.)
According to information summarized by the drug information site Erowid, cannabis has a wide range of positive, neutral, and negative effects. The positive effects include euphoria, relaxation, increased philosophical thinking, greater appreciation of sensory stimuli such as enhanced sound and taste, pleasant bodily sensations, decreased pain and nausea, increased appetite, and decreased boredom. Neutral effects include changes in conscious experience, slowed motor responses, closed eye visual experiences, feeling of sleepiness, difficulty falling asleep, red eye, dry mouth, difficulty thinking in a linear fashion, muscle tension, racing thoughts, and slowed time perception. The negative effects include coughing (when smoking), short term memory difficulties, rapid heart rate, severe anxiety, panic attacks, headache, confusion, paranoia, possible dependency, and the possible precipitation of mental disorders in vulnerable individuals. While marijuana is often thought to have “no hangover” as compared to alcohol, heavy users may experience day after dry mouth, fatigue, drowsiness, and reduced memory. For people who have developed dependency on cannabis a withdrawal syndrome that can last from a few days to many weeks is recognized and includes decreased ability to experience pleasure, headache, poor sleep, decreased appetite, fatigue, and difficulty thinking.
The negative and withdrawal effects noted above probably are related, at least in part, to the fact that THC does cause the release of dopamine from the mesolimbic reward system (Stahl, 2013). While this effect provides some of the pleasure associated with moderate cannabis use, it has the potential to result in problems such as dependency because of the decreased response of the reward system to other sources of pleasure over time (Martz et al, 2016). This is similar to the way in which other drugs that have dependency potential work to produce dependency. Estimating the rates of dependency for various substances is difficult but some older estimates were that around 9 percent of regular cannabis users develop dependency (see Anthony, 2002). These estimates were based during the time of strong cannabis prohibition and do not reflect the effects, positive or negative, of the societal moves to decriminalization and legalization.
In summary, cannabis can have very different psychological effects depending on the make-up of the plant material, the strength and ratio of THC and CBD present, the method of consumption, and the unique features of the individual consuming it. Some of the effects of cannabis seem to hold potential benefit for people suffering from insomnia. These include the reduction of anxiety and the induction of feelings of drowsiness. But cannabis has many other effects and we will have to further investigate how these impact sleep. My next post will explore these issues.
Anthony, J.C. (2002). Epidemiology of drug dependence, in Davis, K.L., Charney, J.T. & Nemeroff, C. (Eds.). (2002). Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia: Lippincott, Williams, & Wilkins.
Bhattacharyya, S., Morrison, P.D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T. Nosarti, T.C., O' Carroll, C.M., Seal, M., Allen, P., Mehta M.A., Stone, J.M., Tunstall, N., Giampietro V., Kapur, K., Murray R.M., Zuardi, A.W., Crippa, J.A., Atakan, Z., & McGuire, P.K. (2010). Opposite effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on human brain function and psychopathology. Neuropsychopharmacology, 35, 764–774; doi:10.1038/npp.2009.184.
Craker, L. E. & Gardner, Z., (2010) in Holland, J. (Ed.). (2010). The Pot Book: A Complete Guide to Cannabis. Santa Cruz, CA: Multidisciplinary Association for Psychedelic Studies.
Gallily, R., Yekhtin, Z. and Hanuš, L.O. (2015) Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy, 6, 75‐85.
Huestis, M. A. (2007). Human Cannabinoid Pharmacokinetics. Chemistry & Biodiversity, 4 (8), 1770–1804. http://doi.org/10.1002/cbdv.200790152
Kim, D. (2012). Practical Use and Risk of Modafinil, a Novel Waking Drug. Environmental Health and Toxicology 2012; 27: e2012007. Published online: February 22, 2012 DOI: https://doi.org/10.5620/eht.2012.27.e2012007
Martz, M.E., Trucco, E.M., Cope, L.M., Hardee, J.E., Jester, J.M., Zucker, R.A., Heitzeg, M.M. (2016). Association of marijuana use with blunted nucleus accumbens response to reward anticipation. JAMA Psychiatry. 2016; 73 (8), 838-844. doi:10.1001/jamapsychiatry.2016.1161
Ramesh, D., Haney, M., & Cooper, Z. D. (2013). Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers. Experimental and Clinical Psychopharmacology, 21 (4), 287–293. http://doi.org/10.1037/a0033661
Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology, Fourth Edition. New York: Cambridge University Press.