There is a potential link between cannabis and mental disorders. Cannabis exposure involves in many cases negative mental emotions, which are unpleasant sensations or thoughts. Whereas mild cases of negative mental emotions inflict patient's quality of life, more severe cases lead to therapy discontinuations, or even hospitalizations and death. This study characterizes cannabis users who experienced negative mental emotions after cannabis exposure. The Releaf App database was utilized to evaluate the association between personal and cannabis use characteristics on reporting a negative mental emotion during cannabis exposure. This global mobile lets individuals track real-time cannabis experience use with cannabinoid-based products, containing data points such as gender, age, reasons for use, product type, cannabis composition, and feelings and emotions experienced after cannabis use. Multivariable logistic regression models were constructed, adjusting for potential confounders such as gender and previous experience with cannabis use. The study population comprised 4,435 users, and 34,279 sessions were collected from various countries, mainly from North America, and included in the primary analysis. Reporting on negative mental emotions was associated with users in the age group of 18-30 years. Using cannabis for a mental purpose was associated with a small increase in reporting on negative mental emotions (OR = 1.10, 95%CI [1.03-1.19]). Oral products were associated with reporting on negative mental emotions. THC-dominant products were associated with reporting negative mental emotions compared to balanced products (OR = 1.21, 95%CI [1.06-1.38]). This study suggests that some characteristics of cannabis use, such as young age and oral consumption are associated with negative mental emotions. Further studies should examine the interface between cannabis consumption, characteristics of consumers, and negative emotional experience or even long-term mental disorders.
Introduction: We measure for the first time the associations between subjective patient experiences of feeling "high" and treatment outcomes during real-time Cannabis flower consumption sessions. Methods: Our study uses data from the mobile health app, Releaf App™, through which 1,882 people tracked the effects of Cannabis flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post-administration symptom intensity levels, total dose used, and real-time side effect experiences. Results: Patients reported feeling high in 49% of cannabis treatment sessions. Using individual patient-level fixed effects regression models and controlling for plant phenotype, consumption mode, tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies, dose, and starting symptom level, our results show that, as compared to sessions in which individuals did not report feeling high, reporting feeling high was associated with a 7.7% decrease in symptom severity from a mean reduction of -3.82 on a 0 to 10 analog scale (coefficient = -0.295, p < 0.001) with evidence of a 14.4 percentage point increase (p < 0.001) in negative side effect reporting and a 4.4 percentage point (p < 0.01) increase in positive side effect reporting. Tetrahydrocannabinol (THC) levels and dose were the strongest statistical predictors of reporting feeling high, while the use of a vaporizer was the strongest inhibitor of feeling high. In symptom-specific models, the association between feeling high and symptom relief remained for people treating pain (p < 0.001), anxiety (p < 0.001), depression (p < 0.01) and fatigue (p < 0.01), but was insignificant, though still negative, for people treating insomnia. Although gender and pre-app cannabis experience did not appear to affect the relationship between high and symptom relief, the relationship was larger in magnitude and more statistically significant among patients aged 40 or less. Discussion: The study results suggest clinicians and policymakers should be aware that feeling high is associated with improved symptom relief but increased negative side effects, and factors such as mode of consumption, product potency, and dose can be used to adjust treatment outcomes for the individual patient.
Objectives: Many annual, nationally representative US surveys that assess cannabis use do not collect information on product characteristics despite varying health risks and benefits. Capitalizing on a rich dataset of primarily medical users, the purpose of this study was to describe the degree of potential misclassification in clinically relevant cannabis use measures when primary mode of use is recorded but not product type. Methods: Analyses consider user-level data from the Releaf App™ database on product types, consumption modes, and potencies in a non-nationally representative sample of 26,322 cannabis administration sessions occurring in 2018, across 3,258 users. Proportions, means, and 95% confidence intervals were calculated and compared across products and modes. Results: Primary consumption modes were smoking (47.1%), vaping (36.5%), and eating/drinking (10.4%), with 22.7% of users reporting multiple modes of use. Moreover, mode of use did not signify a single product type: users reported vaping both flower (41.3%) and concentrates (68.7%). Of those who smoked cannabis, 8.1% reported smoking concentrates. Concentrates averaged 3.4 times higher tetrahydrocannabinol (THC) potency and 3.1 times higher cannabidiol (CBD) potency than flower. Conclusions: Cannabis consumers employ multiple consumption modes, and product type cannot be inferred from mode of use. With THC potencies markedly higher in concentrates, these findings underscore the importance of including information on cannabis product types and mode of use in surveillance surveys. Clinicians and policymakers need these data to inform treatment decisions and assess cannabis policies' implications for population health.
BACKGROUND: Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects. METHODS: Between 09/10/2016 and 03/11/2021, 204 people used the freely available, educational mobile software application, Releaf App, to record 6309 real-time consumption sessions using 633 distinct Cannabis flower products, unique at the user level, with terpene and cannabinoid potency information. The indexing system is based on retrospective data analysis of the products' primary and secondary terpene contents and tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies and yielded a total of 478 distinct chemovars. Analyses of covariances (ANCOVAs) were used to compare symptom levels and side effects experienced across the five most common chemovars before and after cannabis consumption for app users overall and for those treating chronic pain and depression or anxiety. RESULTS: Examination of the five most frequently consumed chemovars showed significant differences in symptom treatment effectiveness for chronic pain and for depression and anxiety (ps < .001). While the effects varied in magnitude, the five chemovars were effective across conditions except for MC61 (mercene .01-0.49%/beta-caryophyllene .01 to 0.49%/THC 20-25%/CBD 0.01-1.0%), which exacerbated feelings of anxiety or depression. The chemovars also differed in their association with experiencing positive, negative, and context-specific side effects, with two chemovars, MC61 and MC62 (mercene .01-0.49%/beta-caryophyllene .01-0.49%/THC 20-25%/CBD 1-5%), generating two to three fewer positive side effects and as much as one more negative and two more context-specific side effects than the other three chemovars. CONCLUSIONS: The findings provide "proof-of-concept" that a simple, yet comprehensive chemovar indexing system can be used to identify systematic differences in clinically relevant patient health outcomes and other common experiences across Cannabis flower products, irrespective of the product's commercial or strain name. This study was limited by self-selection into cannabis and app use and a lack of user-specific information. Further research using this chemovar indexing system should assess how distinct combinations of phytochemicals interact with user-level characteristics to produce general and individualized Cannabis consumption experiences and health outcomes, ideally using randomized methods to assess differences in effects across chemovars.
Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0-10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes ("C. indica," "C. sativa," or "hybrid") did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals' metabolic states and the synergistic chemotypic properties of the plant.
GOALS: We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time. BACKGROUND: Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products. STUDY: Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea. RESULTS: By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of -3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min). CONCLUSIONS: The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.
Antiemetics , Cannabidiol , Cannabis , Medical Marijuana , Analgesics/therapeutic use , Antiemetics/therapeutic use , Cannabidiol/therapeutic use , Child , Dronabinol/therapeutic use , Female , Humans , Medical Marijuana/adverse effects , Nausea/drug therapy , Pregnancy
OBJECTIVE: Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabis products for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache- and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis use. METHODS: Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record real-time details of their Cannabis use, including product characteristics and symptom intensity levels prior to and following self-administration; data included 1910 session-level attempts to treat headache- (1328 sessions) or migraine-related pain (582 sessions). Changes in headache- or migraine-related pain intensity were measured on a 0-10 scale prior to, and immediately, following Cannabis consumption. RESULTS: Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0-10 scale (standard deviation = 2.28, Cohen's d = 1.58), with males experiencing greater relief than females (P < 0.001) and a trend that younger users (< 35 years) experience greater relief than older users (P = 0.08). Mixed effects regression models showed that, among the known (i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers (P < 0.05), females (P < 0.05) and younger users (P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as "C. indica" rather than "C. sativa" or other hybrid strains. CONCLUSION: These results suggest that whole dried Cannabis flower may be an effective medication for treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient.
Cannabis , Headache , Migraine Disorders , Plant Preparations/therapeutic use , Cannabis/chemistry , Dronabinol , Female , Flowers/chemistry , Headache/drug therapy , Humans , Male , Migraine Disorders/drug therapy , United States
Objective: Scientific research on how consumption of whole, natural Cannabis flower affects low mood and behavioral motivations more generally is largely nonexistent, and few studies to date have measured how common and commercially available Cannabis flower used in vivo may affect the experience of "depression" in real-time. Methods: We observed 1,819 people who completed 5,876 cannabis self-administration sessions using the ReleafApp™ between 06/07/2016 and 07/08/2019, with the goal of measuring real-time effects of consuming Cannabis flower for treating symptoms of depression. Results: On average, 95.8% of users experienced symptom relief following consumption with an average symptom intensity reduction of -3.76 points on a 0-10 visual analogue scale (SD = 2.64, d = 1.71, p <.001). Symptom relief did not differ by labeled plant phenotypes ("C. indica," "C. sativa," or "hybrid") or combustion method. Across cannabinoid levels, tetrahydrocannabinol (THC) levels were the strongest independent predictors of symptom relief, while cannabidiol (CBD) levels, instead, were generally unrelated to real-time changes in symptom intensity levels. Cannabis use was associated with some negative side effects that correspond to increased depression (e.g. feeling unmotivated) in up to 20% of users, as well as positive side effects that correspond to decreased depression (e.g. feeling happy, optimistic, peaceful, or relaxed) in up to 64% of users. Conclusions: The findings suggest that, at least in the short term, the vast majority of patients that use cannabis experience antidepressant effects, although the magnitude of the effect and extent of side effect experiences vary with chemotypic properties of the plant.
Affect/drug effects , Antidepressive Agents , Depression , Medical Marijuana , Motivation/drug effects , Adult , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Cannabidiol/blood , Depression/blood , Depression/diagnosis , Depression/drug therapy , Dronabinol/blood , Emotions/drug effects , Female , Humans , Male , Medical Marijuana/administration & dosage , Medical Marijuana/adverse effects , Self Administration/methods , Treatment Outcome , Visual Analog Scale
BACKGROUND: An observational research design was used to evaluate which types of commonly labeled Cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms. METHODS: We used data from 2306 patient-directed cannabis administration sessions among 670 people who used the real-time Cannabis effects recording software, Releaf App, between June 6, 2016, and February 23, 2019, for tracking the effects of Cannabis flower consumption. Fixed effects multivariable panel regression techniques were used to establish overall relief by symptom type and to determine which labeled product characteristics (e.g., subspecies/subtype, inhalation method, and major cannabinoid contents) showed the strongest correlation with changes in momentary feelings of agitation/irritability, anxiety, and stress, along with experienced side effects. RESULTS: In total, a decrease in symptom intensity levels was reported in 95.51% of Cannabis usage sessions, an increase in 2.32% of sessions, and no change in 2.16% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.33 points for agitation/irritability (SE = 0.20, p < 0.01), 3.47 points for anxiety (SE = 0.13, p < 0.01), and 3.98 for stress (SE = 0.12, p < 0.01) on an 11-point visual analog scale. Fixed effects regressions showed that, controlling for time-invariant user characteristics, mid and high tetrahydrocannabinol (THC) levels were the primary independent predictor of increased symptom relief, and that when broken out by symptom type, this effect was only statistically significant for our largest sample of users, those reporting anxiety rather than agitation/irritability or stress. Cannabidiol (CBD) levels were generally not associated with changes in symptom intensity levels. In a minority of cannabis use sessions (< 13%), cannabis users reported anxiogenic-related negative side effects (e.g., feeling anxious, irritable, paranoid, rapid pulse, or restless), whereas in a majority of sessions (about 66%), users reported positive anxiolytic side effects (e.g., feeling chill, comfy, happy, optimistic, peaceful, or relaxed). CONCLUSIONS: The findings suggest the majority of patients in our sample experienced relief from distress-related symptoms following consumption of Cannabis flower, and that among product characteristics, higher THC levels were the strongest predictors of relief.
The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief. Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis' effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was -3.10 points on a 0-10 visual analogue scale (SD = 2.16, d = 1.55, p < .001). Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain. These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.
Cannabis/chemistry , Medical Marijuana/therapeutic use , Pain/drug therapy , Analgesics/adverse effects , Analgesics/therapeutic use , Cannabidiol/adverse effects , Cannabidiol/therapeutic use , Cannabis/adverse effects , Dronabinol/adverse effects , Dronabinol/therapeutic use , Drug-Related Side Effects and Adverse Reactions/etiology , Flowers/chemistry , Humans , Medical Marijuana/adverse effects
Federal barriers and logistical challenges have hindered measurement of the real time effects from the types of cannabis products used medically by millions of patients in vivo. Between 06/06/2016 and 03/05/2018, 3,341 people completed 19,910 self- administrated cannabis sessions using the mobile device software, ReleafApp to record: type of cannabis product (dried whole natural Cannabis flower, concentrate, edible, tincture, topical), combustion method (joint, pipe, vaporization), Cannabis subspecies (C. indica and C. sativa), and major cannabinoid contents (tetrahydrocannabinol, THC; and cannabidiol, CBD), along with real-time ratings of health symptom severity levels, prior-to and immediately following administration, and reported side effects. A fixed effects panel regression approach was used to model the within-user effects of different product characteristics. Patients showed an average symptom improvement of 3.5 (SD = 2.6) on an 11-point scale across the 27 measured symptom categories. Dried flower was the most commonly used product and generally associated with greater symptom relief than other types of products. Across product characteristics, only higher THC levels were independently associated with greater symptom relief and prevalence of positive and negative side effects. In contrast, CBD potency levels were generally not associated with significant symptom changes or experienced side effects.
Cannabidiol/therapeutic use , Cannabinoid Receptor Agonists/therapeutic use , Dronabinol/therapeutic use , Medical Marijuana/therapeutic use , Cannabidiol/administration & dosage , Cannabidiol/adverse effects , Cannabidiol/analysis , Cannabinoid Receptor Agonists/administration & dosage , Cannabinoid Receptor Agonists/adverse effects , Dronabinol/administration & dosage , Dronabinol/adverse effects , Humans , Medical Marijuana/administration & dosage , Medical Marijuana/adverse effects , Psychotropic Drugs/administration & dosage , Psychotropic Drugs/adverse effects , Psychotropic Drugs/therapeutic use , Self Administration
Background: The Releaf AppTM mobile software application (app) data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions. Methods: Between 5/03/2016 and 12/16/2017, 2,830 Releaf AppTM users completed 13,638 individual sessions self-administering medical cannabis and indicated their primary health symptom severity rating on an 11-point (0-10) visual analog scale in real-time prior to and following cannabis consumption, along with experienced side effects. Results: Releaf AppTM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2.8 and 4.6 points (ds ranged from 1.29-2.39, ps < 0.001). On average, higher pre-dosing symptom levels were associated with greater reported symptom relief, and users treating anxiety or depression-related symptoms reported significantly more relief (ps < 0.001) than users with pain symptoms. Of the 42 possible side effects, users were more likely to indicate and showed a stronger correlation between symptom relief and experiences of positive (94% of sessions) or a context-specific side effects (76%), whereas negative side effects (60%) were associated with lessened, yet still significant symptom relief and were more common among patients treating a depressive symptom relative to patients treating anxiety and pain-related conditions. Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.
Background: We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf AppTM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level. Results: Releaf AppTM users showed an average symptom severity reduction of -4.5 points on a 0â»10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes. Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics.
