Addictive Behaviors 50 (2015) 178–181
Contents lists available at ScienceDirect
Addictive Behaviors
Short Communication
Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users Katherine A. Belendiuk a, Kimberly A. Babson b, Ryan Vandrey c, Marcel O. Bonn-Miller b,d,e,f,⁎ a
University of California at Berkeley Institute of Human Development, 1127 Tolman Hall, Berkeley, CA, 94720-1690, USA National Center for PTSD, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA, 94025, USA Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine5510 Nathan Shock Drive, Baltimore, MD, 21224,USA d Center for Innovation to Implementation, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA e Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, Philadelphia, PA, 19104, USA f Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA b c
H I G H L I G H T S • • • •
Individuals using cannabis to manage nightmares preferred sativa to indica. Sativa users were less likely than indica users to endorse cannabis dependence. Insomnia and greater sleep latency are associated with using higher CBD cannabis. Weekly hypnotic medication use is associated with using cannabis with lower THC.
a r t i c l e
i n f o
Article history: Received 22 February 2015 Received in revised form 21 May 2015 Accepted 16 June 2015 Available online 23 June 2015 Keywords: Cannabis Medical marijuana Marijuana Sleep Insomnia
a b s t r a c t Introduction: Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. Methods: 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. Results: 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p b 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (χ2(2) = 4.09, p b 0.05). Individuals with current insomnia (t(9) = 3.30, p b 0.01) and greater sleep latency (F(3,6) = 46.7, p b 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p b 0.05). Conclusions: Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. © 2015 Published by Elsevier Ltd.
1. Introduction The use of cannabis for medical purposes is rapidly expanding, and one of the primary motivations for medicinal cannabis use is to manage sleep difficulties (Bonn-Miller, Boden, Bucossi, & Babson, 2014; Grella,
⁎ Corresponding author at: Center for Innovation to Implementation, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA. E-mail addresses: [email protected] (K.A. Belendiuk), [email protected] (K.A. Babson), [email protected] (R. Vandrey), [email protected] (M.O. Bonn-Miller).
http://dx.doi.org/10.1016/j.addbeh.2015.06.032 0306-4603/© 2015 Published by Elsevier Ltd.
Rodriguez, & Kim, 2014; Walsh et al., 2013). Cannabis may be beneficial in the promotion of sleep (Babson & Bonn-Miller, 2014), though the extent and mechanisms by which cannabis may improve sleep is unclear (Babson & Bonn-Miller, 2014). Some research has suggested that Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of cannabis, is responsible for sleep promotion, while other research has shown Δ9-THC to have an activating effect that can result in poor sleep (Babson & Bonn-Miller, 2014). The primary limitations of existing work on the use and impact of cannabis for sleep promotion are two-fold. First, the majority of work on cannabis and sleep has focused on administration of isolated
K.A. Belendiuk et al. / Addictive Behaviors 50 (2015) 178–181
cannabinoids (e.g., Δ9-THC; Babson & Bonn-Miller, 2014). While this is an important initial step in the literature, cannabis use by the majority of medicinal patients (i.e., smoking the cannabis flower) includes ingestion of a number of additional cannabinoids present in the cannabis plant (e.g., cannabidiol; CBD). Indeed, cannabinoids such as CBD have both psychoactive and non-psychoactive properties, which may interact with Δ9-THC to produce more nuanced effects (Aizpurua-Olaizola et al., 2014; Englund et al., 2013; Russo, 2011; Vann et al., 2008; Walsh et al., 2013; Zuardi, Hallak, & Crippa, 2012). Similarly, there is a lack of naturalistic observation of cannabis use behavior among those with self-reported sleep problems. Studies have examined sleep effects following laboratory administration of cannabinoids, but laboratorybased studies do not necessarily translate to “real world” behaviors as cannabis choice is not afforded within the laboratory context (Burgdorf, Kilmer, & Pacula, 2011; Mitchell, 2012). As such, it is necessary to document naturalistic choice of particular medical cannabis types among individuals who self-report using cannabis for the treatment of sleep problems. Cannabis can be categorized by plant sub-species that, within species, can vary considerably with regard to relative cannabinoid concentration. Cannabis strains obtained at dispensaries within the U.S. are typically classified as one of 3 species designations: indica, sativa, and “hybrid” (cross-bred cannabis plants containing characteristics of both indica and sativa varieties). However, little is known regarding differences between indica and sativa in terms of psychoactive effects or variations in cannabinoid concentration (i.e., amount of each cannabinoid). Indeed, cannabinoid concentration can vary widely between cannabis flowers obtained and used by medicinal patients (Hillig & Mahlberg, 2004). Furthermore, little research has documented species or cannabinoid concentration preferences among individuals who use medical cannabis for particular conditions. The purpose of the present study was to document cannabis species and cannabinoid concentration preferences among medical cannabis users who report using cannabis for the management of sleep problems. Because individuals who use cannabis to improve sleep have been shown to be at increased risk for the experience of negative consequences associated with use (Bonn-Miller, Babson, & Vandrey, 2014), we also evaluated the interaction between the type of cannabis used and diagnosis of cannabis use disorder among study participants.
179
(97%), 39% completed a 2- or 4-year college degree, and 15% had an advanced degree. Participants reported using cannabis for medical purposes for an average of 10.8 years (SD = 10.4, range = 2 months–47 years). 2.3. Measures 2.3.1. Medical use of cannabis The conditions for which participants were using cannabis, and the strains of cannabis that were most used for these conditions, were assessed with the Medical Marijuana Patient Use Questionnaire (MMPUQ; see Bonn-Miller, Boden, Bucossi, & Babson, 2014). Participants were asked “What condition(s) have led you to seek out medical cannabis (i.e., what is it prescribed for)?” Sleep-related response options for this item included “insomnia” and “nightmares;” other medical conditions treated with cannabis are discussed by Bonn-Miller, Boden, Bucossi, and Babson (2014). An additional question asked participants to list the names of up to four types of cannabis that they used. Names of the cannabis types provided were matched with dispensary data to identify the cannabis species (i.e. sativa, indica, or hybrid), and the concentrations of THC and CBD. Hybrid plant strains were sub-divided into those that were considered primarily sativa and those considered primarily indica, indicating the dominant species for each plant. Cannabis flower concentrations of THC and CBD were batch tested by the dispensary upon receipt, with testing information (e.g., THC concentration) posted on the dispensary website. Not all cannabis varieties were tested for cannabinoid concentration by the dispensary, though those that were chosen for testing were tested regularly and upon receipt of each new batch. Individual cannabis preference was determined by a count of the species most frequently endorsed from strains reported (e.g. if a participant reported using three sativa/primary sativa hybrid strains and one indica/primary indica hybrid strain, they were said to prefer sativa). 2.3.2. Cannabis use disorder Cannabis use disorder (CUD) diagnosis was assessed using the Structured Clinical Interview-Non-Patient Version for DSM-IV (SCID-I-N/P; First, Spitzer, Gibbon, & Williams, 1995), modified to be consistent with DSM-5 (see Budney, Hughes, Moore, & Vandrey, 2004). Cronbach's α was .72.
2. Method 2.1. Procedure Patients of a medical cannabis dispensary located in California were recruited for the current study. Study staff manned a table in the dispensary two days per week in 2012, and provided patrons with a flyer with study information as they entered. For those who were interested, study procedures were explained and written informed consent was obtained. Individuals under the age of 18 years or unable to provide written informed consent to participate were excluded. Participants completed a series of self-report questionnaires, were debriefed, and then entered into one of four weekly drawings for $100 as compensation for participation. Procedures were approved by the VA and Stanford University institutional review boards. 2.2. Participants Of the 217 adults (73% male) who participated in a larger study (Bonn-Miller, Boden, Bucossi, & Babson, 2014), 163 provided information on the specific strains of cannabis used for the treatment of their medical or psychiatric disorder(s) and were included in the current study. The mean age of participants was 40.4 (SD = 14.3, range 18–73 years). Most participants were White/Caucasian (67.1%), followed by Black/ Non-Hispanic (7.5%), Hispanic (6.8%), Black/Hispanic (3.7%), Asian (3.1%), and “Other” (11.8%). Most had at least a high school education
2.3.3. Sleep problems Self-reported sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). The PSQI is a 19-item questionnaire that provides an index of global sleep quality and seven components of sleep quality. Cronbach's α for the global score was .87 (Backhaus, Junghanns, Broocks, Riemann, & Hohagen, 2002). 2.4. Analytic plan Fisher's exact test was used to identify whether species preference was associated with binary sleep problems (i.e. nightmares and insomnia). T-tests for binary sleep variables, ANOVAs for categorical or ordinal sleep variables, and correlations for continuous sleep variables were used to evaluate relationships between sleep variables and cannabis (i.e. THC and CBD) concentration. Logistic regression was used to regress CUD on age and χ2 testing was used to examine associations between CUD and strain preference. 3. Results 3.1. Sample characteristics On average, participants reported using cannabis nearly twice a day during the past month (M = 58.7 times per month; SD = 65; range =
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K.A. Belendiuk et al. / Addictive Behaviors 50 (2015) 178–181
0–640); only 5% of the sample reported using cannabis more than 4 times a day, on average. There was no association between frequency of cannabis use and nightmares (t(148) = −0.11, p = 0.91), insomnia (t(148) = − 0.57, p = 0.57), or strain preference (F(34,115) = 0.77, p = 0.81). Participants reported using 4.3 grams of cannabis per occasion (SD = 2.3; range = 1–8), on average. The sativa/primary sativa hybrid was the preferred species for 62 (38%) participants, 46 (28%) preferred indica/primary indica hybrid strains, and 55 (34%) reported using indica/primary indica hybrids and sativa/primary sativa hybrids with equal frequency. For the 75 participants for whom THC concentration could be ascertained, the average concentration was 19% (SD = 5.8; range = 1–25). For the 11 participants for whom CBD concentration could be ascertained, the average concentration was 7% (SD = 5.9; range = 0.22–16). THC concentration was significantly higher among strains classified as indica compared with those classified as sativa (t(71) = 2.06, p b 0.05). 47% of the sample met criteria for CUD. Half of study participants reported using cannabis to help treat symptoms of insomnia, and 14 (9%) reported using cannabis to manage nightmares. On the PSQI, participants endorsed an average global sleep quality score of 7.52 (SD = 3.63) with 19.9% meeting criteria for sleep dysfunction (PSQI N 5). In the month prior to survey completion, 22.8% reported poor sleep quality, 69.1% of individuals had a mean sleep latency of greater than 30 minutes, 19.5% reported a mean total sleep duration of less than 6 hours per night, 34.2% reported a sleep efficiency (time asleep/time in bed) of less than 75%, 52.1% reported significant sleep disturbances at least 1–2 times per week, and 25.9% reported the use of hypnotic medication within the past month. Finally, 14.4% endorsed daytime functional impairment as a consequence of poor sleep at least 1–2 times per week.
3.2. Sleep problems and species preference Individuals who reported using cannabis for nightmares, compared to those who did not, preferred sativa to indica (Fisher's exact test (2) = 6.83, p b 0.05). This was a small effect (Cramèr's V = 0.22). There were no differences in cannabis species preference as a function of self-reported sleep quality, or use for insomnia. 3.3. Sleep problems and cannabinoid concentration Individuals who used sleep medication less than once/week (N = 57) used cannabis with higher THC concentrations than those who used sleep medication at least once a week (N = 15; t(17) = 2.40, p b 0.05). This was a large effect (Cohen's d = 0.89). There were no differences in THC concentration as a function self-reported sleep quality, or use for insomnia or nightmares. Individuals who self-report using cannabis to treat symptoms of insomnia (t(9) = 3.30, p b 0.01; Cohen's d = 2.00) and those with greater self-reported sleep latency on the PSQI (F(3,6) = 46.7, p b 0.001; η2 = 0.96) reported using cannabis with significantly higher concentrations of CBD. These were both large effects. There were no differences in concentration of CBD as a function of self-reported sleep quality or use for nightmares.
4. Discussion The present study was the first to examine preferences of cannabis species and cannabinoid concentration among individuals specifically using cannabis for the management of sleep problems. While previous research has shown that individuals use cannabis to help manage sleep problems (Babson & Bonn-Miller, 2014), the current findings extend this work by highlighting individual naturalistic preference of cannabis species and cannabinoid concentration as a function of selfreported sleep disorder/quality, including corresponding relations to CUD. Individuals who reported using sleep medications at a lower frequency used cannabis with higher concentrations of THC. This was somewhat unexpected, as higher THC concentrations have been shown to have a stimulating effect that can lead to poor sleep (Babson & Bonn-Miller, 2014). It is unknown whether participants in the present study used this type of cannabis during the day and avoided cannabis use prior to bedtime, or whether they had developed tolerance to the stimulating effects of high THC cannabis. Indeed, higher THC concentration was also associated with greater rates of CUD, suggesting that tolerance may be a factor. In contrast, individuals using cannabis to reduce nightmares were more likely to use a species of cannabis (i.e. sativa) that was associated with a lower risk of CUD. This study also replicates prior findings highlighting a decrease in CUD prevalence with age (Compton, Grant, Colliver, Glantz, & Stinson, 2004), and reinforces the importance of early screening and intervention for youth who may be most vulnerable to the long-term impact of early cannabis use. Although there were several strengths to the current study, it was not without limitation. The present study relied on retrospective reports of sleep quality and cannabis preference, cannabinoid concentration was not available for all types of cannabis used, and cannabinoid constituency was limited to concentrations of THC and CBD. Future studies would benefit from prospectively evaluating well-characterized strains of each cannabis species. Additionally, while the present study is an important first step in understanding how individuals with sleep dysfunction use cannabis, more information is needed to elucidate shared variables that may predict sleep dysfunction, preferences in cannabis characteristics, and CUD. One important future direction is to examine potential third variables, including PTSD and co-occurring substance use. Additional research is needed to elucidate the effect of cannabis species and cannabinoid concentration (e.g. THC and CBD) on the safety and efficacy of cannabis for the management of sleep problems. Role of funding source Funding was provided by a donation from the San Francisco Patient and Resource Center. Dr. Belendiuk's salary was supported by National Institute of Mental Health R01 MH40564. Dr. Bonn-Miller's salary was supported by the VA Center of Excellence for Substance Abuse Treatment and Education.
Contributors Dr. Belendiuk conducted statistical analysis and authored sections of the manuscript. Dr. Babson authored sections of the manuscript. Dr. Vandrey authored sections of the manuscript. Dr. Bonn-Miller oversaw collection of data, conceived the manuscript, and authored sections of the manuscript.
3.4. Strain characteristics and cannabis use disorder Older individuals (B = −0.05, SE = 0.012, p = 0.00) were less likely to have CUD compared to those younger. Every one year increase in age resulted in a 0.95 (CI95 = 0.93 to 0.98) decrease in CUD. Additionally, individuals who preferred sativa or primary sativa hybrid strains (χ2(2) = 4.09, p b 0.05) were less likely to have CUD compared to those who preferred indica or primary indica hybrid strains; this was a small effect (Cramèr's V = 0.12). Neither concentration of THC nor CBD were associated with CUD.
Conflict of interest No conflicts declared
Acknowledgments Funding was provided by a donation from the San Francisco Patient and Resource Center. Dr. Belendiuk's salary was supported by National Institute of Mental Health R01 MH40564. This work was supported, in part, by a VA Clinical Science Research and Development (CSR&D) Career Development Award (CDA-2; 1IK2CX1023-01A1) awarded to Dr. Babson.
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References Aizpurua-Olaizola, O., Omar, J., Navarro, P., Olivares, M., Etxebarria, N., & Usobiaga, A. (2014). Identification and quantification of cannabinoids in Cannabis sativa L. plants by high performance liquid chromatography-mass spectrometry. Analytical and Bioanalytical Chemistry, 406, 7549–7560. Babson, K.A., & Bonn-Miller, M.O. (2014). Sleep disturbances: Implications for cannabis use, cannabis use cessation, and cannabis use treatment. Current Addiction Reports, 1, 109–114. Backhaus, J., Junghanns, K., Broocks, A., Riemann, D., & Hohagen, F. (2002). Test–retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. Journal of Psychosomatic Research, 53, 737–740. Bonn-Miller, M.O., Babson, K.A., & Vandrey, R. (2014). Using cannabis to help you sleep: Heightened frequency of medical cannabis use among those with PTSD. Drug and Alcohol Dependence, 136, 162–165. Bonn-Miller, M.O., Boden, M.T., Bucossi, M.M., & Babson, K.A. (2014). Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users. American Journal of Drug and Alcohol Abuse, 40, 23–30. Budney, A.J., Hughes, J.R., Moore, B.A., & Vandrey, R. (2004). Review of the validity and significance of cannabis withdrawal syndrome. The American Journal of Psychiatry, 161, 1967–1977. Burgdorf, J.R., Kilmer, B., & Pacula, R.L. (2011). Heterogeneity in the composition of marijuana seized in California. Drug and Alcohol Dependence, 117, 59–61. Buysse, D.J., Reynolds, C.F., Monk, T.H., Berman, S.R., & Kupfer, D.J. (1989). The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Research, 28, 193–213. Compton, W.M., Grant, B.F., Colliver, J.D., Glantz, M.D., & Stinson, F.S. (2004). Prevalence of marijuana use disorders in the United States: 1991–1992 and 2001–2002. JAMA, 291, 2114–2121.
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Englund, A., Morrison, P.D., Nottage, J., Hague, D., Kane, F., Bonaccorso, S., et al. (2013). Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of Psychopharmacology, 27, 19–27. First, M.B., Spitzer, R.L., Gibbon, M., & Williams, J. (1995). Structured Clinical Interview for DSM-IV axis I disorders- non-patient edition. New York: New York State Psychiatric Institute. Grella, C.E., Rodriguez, L., & Kim, T. (2014). Patterns of medical marijuana use among individuals sampled from medical marijuana dispensaries in Los Angeles. Journal of Psychoactive Drugs, 46, 263–272. Hillig, K.W., & Mahlberg, P.G. (2004). A chemotaxonomic analysis of cannabinoid variation in Cannabis (cannabaceae). American Journal of Botany, 91, 966–975. Mitchell, G. (2012). Revisiting truth or triviality: The external validity of research in the psychological laboratory. Perspectives on Psychological Science, 7, 109–117. Russo, E.B. (2011). Taming THC: Potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British Journal of Pharmacology, 163, 1344–1364. Vann, R.E., Gamage, T.F., Warner, J.A., Marshall, E.M., Taylor, N.L., Martin, B.R., et al. (2008). Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ(9)-tetrahydrocannabinol. Drug and Alcohol Dependence, 94, 191–198. Walsh, Z., Callaway, R., Belle-Isle, L., Capler, R., Kay, R., Lucas, P., et al. (2013). Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use. International Journal of Drug Policy, 24, 511–516. Zuardi, A.W., Hallak, J.E., & Crippa, J.A. (2012). Interaction between cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology, 219, 247–249.
Contents lists available at ScienceDirect
Addictive Behaviors
Short Communication
Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users Katherine A. Belendiuk a, Kimberly A. Babson b, Ryan Vandrey c, Marcel O. Bonn-Miller b,d,e,f,⁎ a
University of California at Berkeley Institute of Human Development, 1127 Tolman Hall, Berkeley, CA, 94720-1690, USA National Center for PTSD, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA, 94025, USA Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine5510 Nathan Shock Drive, Baltimore, MD, 21224,USA d Center for Innovation to Implementation, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA e Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, Philadelphia, PA, 19104, USA f Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA b c
H I G H L I G H T S • • • •
Individuals using cannabis to manage nightmares preferred sativa to indica. Sativa users were less likely than indica users to endorse cannabis dependence. Insomnia and greater sleep latency are associated with using higher CBD cannabis. Weekly hypnotic medication use is associated with using cannabis with lower THC.
a r t i c l e
i n f o
Article history: Received 22 February 2015 Received in revised form 21 May 2015 Accepted 16 June 2015 Available online 23 June 2015 Keywords: Cannabis Medical marijuana Marijuana Sleep Insomnia
a b s t r a c t Introduction: Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. Methods: 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. Results: 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p b 0.05), and sativa users were less likely to endorse DSM-5 cannabis dependence compared with those who preferred indica strains (χ2(2) = 4.09, p b 0.05). Individuals with current insomnia (t(9) = 3.30, p b 0.01) and greater sleep latency (F(3,6) = 46.7, p b 0.001) were more likely to report using strains of cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p b 0.05). Conclusions: Associations between sleep characteristics and the type of cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. © 2015 Published by Elsevier Ltd.
1. Introduction The use of cannabis for medical purposes is rapidly expanding, and one of the primary motivations for medicinal cannabis use is to manage sleep difficulties (Bonn-Miller, Boden, Bucossi, & Babson, 2014; Grella,
⁎ Corresponding author at: Center for Innovation to Implementation, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA. E-mail addresses: [email protected] (K.A. Belendiuk), [email protected] (K.A. Babson), [email protected] (R. Vandrey), [email protected] (M.O. Bonn-Miller).
http://dx.doi.org/10.1016/j.addbeh.2015.06.032 0306-4603/© 2015 Published by Elsevier Ltd.
Rodriguez, & Kim, 2014; Walsh et al., 2013). Cannabis may be beneficial in the promotion of sleep (Babson & Bonn-Miller, 2014), though the extent and mechanisms by which cannabis may improve sleep is unclear (Babson & Bonn-Miller, 2014). Some research has suggested that Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of cannabis, is responsible for sleep promotion, while other research has shown Δ9-THC to have an activating effect that can result in poor sleep (Babson & Bonn-Miller, 2014). The primary limitations of existing work on the use and impact of cannabis for sleep promotion are two-fold. First, the majority of work on cannabis and sleep has focused on administration of isolated
K.A. Belendiuk et al. / Addictive Behaviors 50 (2015) 178–181
cannabinoids (e.g., Δ9-THC; Babson & Bonn-Miller, 2014). While this is an important initial step in the literature, cannabis use by the majority of medicinal patients (i.e., smoking the cannabis flower) includes ingestion of a number of additional cannabinoids present in the cannabis plant (e.g., cannabidiol; CBD). Indeed, cannabinoids such as CBD have both psychoactive and non-psychoactive properties, which may interact with Δ9-THC to produce more nuanced effects (Aizpurua-Olaizola et al., 2014; Englund et al., 2013; Russo, 2011; Vann et al., 2008; Walsh et al., 2013; Zuardi, Hallak, & Crippa, 2012). Similarly, there is a lack of naturalistic observation of cannabis use behavior among those with self-reported sleep problems. Studies have examined sleep effects following laboratory administration of cannabinoids, but laboratorybased studies do not necessarily translate to “real world” behaviors as cannabis choice is not afforded within the laboratory context (Burgdorf, Kilmer, & Pacula, 2011; Mitchell, 2012). As such, it is necessary to document naturalistic choice of particular medical cannabis types among individuals who self-report using cannabis for the treatment of sleep problems. Cannabis can be categorized by plant sub-species that, within species, can vary considerably with regard to relative cannabinoid concentration. Cannabis strains obtained at dispensaries within the U.S. are typically classified as one of 3 species designations: indica, sativa, and “hybrid” (cross-bred cannabis plants containing characteristics of both indica and sativa varieties). However, little is known regarding differences between indica and sativa in terms of psychoactive effects or variations in cannabinoid concentration (i.e., amount of each cannabinoid). Indeed, cannabinoid concentration can vary widely between cannabis flowers obtained and used by medicinal patients (Hillig & Mahlberg, 2004). Furthermore, little research has documented species or cannabinoid concentration preferences among individuals who use medical cannabis for particular conditions. The purpose of the present study was to document cannabis species and cannabinoid concentration preferences among medical cannabis users who report using cannabis for the management of sleep problems. Because individuals who use cannabis to improve sleep have been shown to be at increased risk for the experience of negative consequences associated with use (Bonn-Miller, Babson, & Vandrey, 2014), we also evaluated the interaction between the type of cannabis used and diagnosis of cannabis use disorder among study participants.
179
(97%), 39% completed a 2- or 4-year college degree, and 15% had an advanced degree. Participants reported using cannabis for medical purposes for an average of 10.8 years (SD = 10.4, range = 2 months–47 years). 2.3. Measures 2.3.1. Medical use of cannabis The conditions for which participants were using cannabis, and the strains of cannabis that were most used for these conditions, were assessed with the Medical Marijuana Patient Use Questionnaire (MMPUQ; see Bonn-Miller, Boden, Bucossi, & Babson, 2014). Participants were asked “What condition(s) have led you to seek out medical cannabis (i.e., what is it prescribed for)?” Sleep-related response options for this item included “insomnia” and “nightmares;” other medical conditions treated with cannabis are discussed by Bonn-Miller, Boden, Bucossi, and Babson (2014). An additional question asked participants to list the names of up to four types of cannabis that they used. Names of the cannabis types provided were matched with dispensary data to identify the cannabis species (i.e. sativa, indica, or hybrid), and the concentrations of THC and CBD. Hybrid plant strains were sub-divided into those that were considered primarily sativa and those considered primarily indica, indicating the dominant species for each plant. Cannabis flower concentrations of THC and CBD were batch tested by the dispensary upon receipt, with testing information (e.g., THC concentration) posted on the dispensary website. Not all cannabis varieties were tested for cannabinoid concentration by the dispensary, though those that were chosen for testing were tested regularly and upon receipt of each new batch. Individual cannabis preference was determined by a count of the species most frequently endorsed from strains reported (e.g. if a participant reported using three sativa/primary sativa hybrid strains and one indica/primary indica hybrid strain, they were said to prefer sativa). 2.3.2. Cannabis use disorder Cannabis use disorder (CUD) diagnosis was assessed using the Structured Clinical Interview-Non-Patient Version for DSM-IV (SCID-I-N/P; First, Spitzer, Gibbon, & Williams, 1995), modified to be consistent with DSM-5 (see Budney, Hughes, Moore, & Vandrey, 2004). Cronbach's α was .72.
2. Method 2.1. Procedure Patients of a medical cannabis dispensary located in California were recruited for the current study. Study staff manned a table in the dispensary two days per week in 2012, and provided patrons with a flyer with study information as they entered. For those who were interested, study procedures were explained and written informed consent was obtained. Individuals under the age of 18 years or unable to provide written informed consent to participate were excluded. Participants completed a series of self-report questionnaires, were debriefed, and then entered into one of four weekly drawings for $100 as compensation for participation. Procedures were approved by the VA and Stanford University institutional review boards. 2.2. Participants Of the 217 adults (73% male) who participated in a larger study (Bonn-Miller, Boden, Bucossi, & Babson, 2014), 163 provided information on the specific strains of cannabis used for the treatment of their medical or psychiatric disorder(s) and were included in the current study. The mean age of participants was 40.4 (SD = 14.3, range 18–73 years). Most participants were White/Caucasian (67.1%), followed by Black/ Non-Hispanic (7.5%), Hispanic (6.8%), Black/Hispanic (3.7%), Asian (3.1%), and “Other” (11.8%). Most had at least a high school education
2.3.3. Sleep problems Self-reported sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). The PSQI is a 19-item questionnaire that provides an index of global sleep quality and seven components of sleep quality. Cronbach's α for the global score was .87 (Backhaus, Junghanns, Broocks, Riemann, & Hohagen, 2002). 2.4. Analytic plan Fisher's exact test was used to identify whether species preference was associated with binary sleep problems (i.e. nightmares and insomnia). T-tests for binary sleep variables, ANOVAs for categorical or ordinal sleep variables, and correlations for continuous sleep variables were used to evaluate relationships between sleep variables and cannabis (i.e. THC and CBD) concentration. Logistic regression was used to regress CUD on age and χ2 testing was used to examine associations between CUD and strain preference. 3. Results 3.1. Sample characteristics On average, participants reported using cannabis nearly twice a day during the past month (M = 58.7 times per month; SD = 65; range =
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0–640); only 5% of the sample reported using cannabis more than 4 times a day, on average. There was no association between frequency of cannabis use and nightmares (t(148) = −0.11, p = 0.91), insomnia (t(148) = − 0.57, p = 0.57), or strain preference (F(34,115) = 0.77, p = 0.81). Participants reported using 4.3 grams of cannabis per occasion (SD = 2.3; range = 1–8), on average. The sativa/primary sativa hybrid was the preferred species for 62 (38%) participants, 46 (28%) preferred indica/primary indica hybrid strains, and 55 (34%) reported using indica/primary indica hybrids and sativa/primary sativa hybrids with equal frequency. For the 75 participants for whom THC concentration could be ascertained, the average concentration was 19% (SD = 5.8; range = 1–25). For the 11 participants for whom CBD concentration could be ascertained, the average concentration was 7% (SD = 5.9; range = 0.22–16). THC concentration was significantly higher among strains classified as indica compared with those classified as sativa (t(71) = 2.06, p b 0.05). 47% of the sample met criteria for CUD. Half of study participants reported using cannabis to help treat symptoms of insomnia, and 14 (9%) reported using cannabis to manage nightmares. On the PSQI, participants endorsed an average global sleep quality score of 7.52 (SD = 3.63) with 19.9% meeting criteria for sleep dysfunction (PSQI N 5). In the month prior to survey completion, 22.8% reported poor sleep quality, 69.1% of individuals had a mean sleep latency of greater than 30 minutes, 19.5% reported a mean total sleep duration of less than 6 hours per night, 34.2% reported a sleep efficiency (time asleep/time in bed) of less than 75%, 52.1% reported significant sleep disturbances at least 1–2 times per week, and 25.9% reported the use of hypnotic medication within the past month. Finally, 14.4% endorsed daytime functional impairment as a consequence of poor sleep at least 1–2 times per week.
3.2. Sleep problems and species preference Individuals who reported using cannabis for nightmares, compared to those who did not, preferred sativa to indica (Fisher's exact test (2) = 6.83, p b 0.05). This was a small effect (Cramèr's V = 0.22). There were no differences in cannabis species preference as a function of self-reported sleep quality, or use for insomnia. 3.3. Sleep problems and cannabinoid concentration Individuals who used sleep medication less than once/week (N = 57) used cannabis with higher THC concentrations than those who used sleep medication at least once a week (N = 15; t(17) = 2.40, p b 0.05). This was a large effect (Cohen's d = 0.89). There were no differences in THC concentration as a function self-reported sleep quality, or use for insomnia or nightmares. Individuals who self-report using cannabis to treat symptoms of insomnia (t(9) = 3.30, p b 0.01; Cohen's d = 2.00) and those with greater self-reported sleep latency on the PSQI (F(3,6) = 46.7, p b 0.001; η2 = 0.96) reported using cannabis with significantly higher concentrations of CBD. These were both large effects. There were no differences in concentration of CBD as a function of self-reported sleep quality or use for nightmares.
4. Discussion The present study was the first to examine preferences of cannabis species and cannabinoid concentration among individuals specifically using cannabis for the management of sleep problems. While previous research has shown that individuals use cannabis to help manage sleep problems (Babson & Bonn-Miller, 2014), the current findings extend this work by highlighting individual naturalistic preference of cannabis species and cannabinoid concentration as a function of selfreported sleep disorder/quality, including corresponding relations to CUD. Individuals who reported using sleep medications at a lower frequency used cannabis with higher concentrations of THC. This was somewhat unexpected, as higher THC concentrations have been shown to have a stimulating effect that can lead to poor sleep (Babson & Bonn-Miller, 2014). It is unknown whether participants in the present study used this type of cannabis during the day and avoided cannabis use prior to bedtime, or whether they had developed tolerance to the stimulating effects of high THC cannabis. Indeed, higher THC concentration was also associated with greater rates of CUD, suggesting that tolerance may be a factor. In contrast, individuals using cannabis to reduce nightmares were more likely to use a species of cannabis (i.e. sativa) that was associated with a lower risk of CUD. This study also replicates prior findings highlighting a decrease in CUD prevalence with age (Compton, Grant, Colliver, Glantz, & Stinson, 2004), and reinforces the importance of early screening and intervention for youth who may be most vulnerable to the long-term impact of early cannabis use. Although there were several strengths to the current study, it was not without limitation. The present study relied on retrospective reports of sleep quality and cannabis preference, cannabinoid concentration was not available for all types of cannabis used, and cannabinoid constituency was limited to concentrations of THC and CBD. Future studies would benefit from prospectively evaluating well-characterized strains of each cannabis species. Additionally, while the present study is an important first step in understanding how individuals with sleep dysfunction use cannabis, more information is needed to elucidate shared variables that may predict sleep dysfunction, preferences in cannabis characteristics, and CUD. One important future direction is to examine potential third variables, including PTSD and co-occurring substance use. Additional research is needed to elucidate the effect of cannabis species and cannabinoid concentration (e.g. THC and CBD) on the safety and efficacy of cannabis for the management of sleep problems. Role of funding source Funding was provided by a donation from the San Francisco Patient and Resource Center. Dr. Belendiuk's salary was supported by National Institute of Mental Health R01 MH40564. Dr. Bonn-Miller's salary was supported by the VA Center of Excellence for Substance Abuse Treatment and Education.
Contributors Dr. Belendiuk conducted statistical analysis and authored sections of the manuscript. Dr. Babson authored sections of the manuscript. Dr. Vandrey authored sections of the manuscript. Dr. Bonn-Miller oversaw collection of data, conceived the manuscript, and authored sections of the manuscript.
3.4. Strain characteristics and cannabis use disorder Older individuals (B = −0.05, SE = 0.012, p = 0.00) were less likely to have CUD compared to those younger. Every one year increase in age resulted in a 0.95 (CI95 = 0.93 to 0.98) decrease in CUD. Additionally, individuals who preferred sativa or primary sativa hybrid strains (χ2(2) = 4.09, p b 0.05) were less likely to have CUD compared to those who preferred indica or primary indica hybrid strains; this was a small effect (Cramèr's V = 0.12). Neither concentration of THC nor CBD were associated with CUD.
Conflict of interest No conflicts declared
Acknowledgments Funding was provided by a donation from the San Francisco Patient and Resource Center. Dr. Belendiuk's salary was supported by National Institute of Mental Health R01 MH40564. This work was supported, in part, by a VA Clinical Science Research and Development (CSR&D) Career Development Award (CDA-2; 1IK2CX1023-01A1) awarded to Dr. Babson.
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