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Cannabinoid Exposure and Subjective Effects of THC and CBD in Edible Cannabis Products

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Abstract

Background: The popularity of edible cannabis products continues to grow in states with legal cannabis access, but few studies have investigated the acute effects of these commercially available products. The present study sought to explore the effects of three commercially available edible products with different levels of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Methods: A sample of regular cannabis users (N=99) were evaluated. Fifty participants completed the study procedures in-person, whereas 49 participants completed the study procedures remotely via Zoom. Subjective effects and plasma cannabinoid levels (in-person participants only) were assessed before and 2 h after participants self-administered one of three products ad libitum: a THC-dominant edible product, a CBD-dominant edible product, or a THC+CBD edible product. Results: At the 2-h post-use assessment, among in-person participants, plasma THC and CBD levels were robustly correlated with self-reported milligrams of THC and CBD consumed, respectively. Across all three conditions, in-person and remote participants experienced (1) an increase in subjective intoxication and elation, (2) a decrease in tension, and (3) no change in paranoia from pre-use to post-use. At post-use, participants who used a CBD product reported less intoxication relative to participants who used a THC+CBD or THC-only product. Participants who used a THC+CBD product reported consuming less THC-and displayed lower plasma THC levels (in-person participants)-relative to participants who used a THC-only product, despite reporting similar levels of positive (intoxication, elation, liking) and psychotomimetic (paranoia, tension) effects. Psychotomimetic effects were very low among both in-person and remote participants across all three conditions, and there were no post-use differences across conditions. Conclusions: Findings suggest that experienced users who consumed a THC+CBD product reported similar levels of positive and psychotomimetic effects relative to those who consumed a THC-only product, despite consuming less THC and displaying lower plasma THC concentrations. Given the potential harms associated with acute cannabis reward and long-term THC exposure, further research is needed to establish whether edible cannabis products with CBD pose less risk to users. Future studies should examine whether these effects generalize to samples of infrequent users, who may have less experience with edible cannabis use. ClinicalTrials.gov ID: NCT03522103.

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Background: Cannabis varies considerably in levels of its two major constituent cannabinoids - (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being. Method: A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety. Results: Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair. Conclusions: CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as 'skunk' (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.
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Anxiety reactions and panic attacks are the acute symptoms most frequently associated with cannabis use. Understanding the relationship between cannabis and anxiety may clarify the mechanism of action of cannabis and the pathophysiology of anxiety. Aims of the present study were to review the nature of the relationship between cannabis use and anxiety, as well as the possible clinical, diagnostic and causal implications. Systematic review of the Medline, PsycLIT and EMBASE literature. Frequent cannabis users consistently have a high prevalence of anxiety disorders and patients with anxiety disorders have relatively high rates of cannabis use. However, it is unclear if cannabis use increases the risk of developing long-lasting anxiety disorders. Many hypotheses have been proposed in an attempt to explain these relationships, including neurobiological, environmental and social influences. The precise relationship between cannabis use and anxiety has yet to be established. Research is needed to fully clarify the mechanisms of such the association.
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The purpose of this study was to identify circumstances in which biochemical assessments of smoking produce systematically higher or lower estimates of smoking than self-reports. A secondary aim was to evaluate different statistical approaches to analyzing variation in validity estimates. Literature searches and personal inquiries identified 26 published reports containing 51 comparisons between self-reported behavior and biochemical measures. The sensitivity and specificity of self-reports of smoking were calculated for each study as measures of accuracy. Sensitivity ranged from 6% to 100% (mean = 87.5%), and specificity ranged from 33% to 100% (mean = 89.2%). Interviewer-administered questionnaires, observational studies, reports by adults, and biochemical validation with cotinine plasma were associated with higher estimates of sensitivity and specificity. Self-reports of smoking are accurate in most studies. To improve accuracy, biochemical assessment, preferably with cotinine plasma, should be considered in intervention studies and student populations.
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Although some aspects of memory functions are known to be acutely impaired by delta(9)-tetrahydrocannabinol (delta(9)-THC; the main active constituent of marijuana), effects on other aspects of memory are not known and the time course of functional impairments is unclear. The present study aimed to detail the acute and residual cognitive effects of delta(9)-THC in infrequent cannabis users. A balanced, double-blind cross-over design was used to compare the effects of 7.5 mg and 15 mg delta(9)-THC with matched placebo in 15 male volunteers. Participants were assessed pre and 1, 2, 4, 6, 8, 24 and 48 h post-drug. Delta(9)-THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration (2 h post-drug). At the same time point, performance on an implicit memory task was preserved intact. The higher dose of delta(9)-THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by delta(9)-THC. In several tasks, delta(9)-THC increased both speed and error rates, reflecting "riskier" speed-accuracy trade-offs. Subjective effects were also most marked at 2 h but often persisted longer, with participants rating themselves as "stoned" for 8 h. Participants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral delta(9)-THC. No effects of delta(9)-THC were found 24 or 48 h following ingestion indicating that the residual effects of oral delta(9)-THC are minimal. These data demonstrate that oral delta(9)-THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory.
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Although smoked marijuana contains at least 60 cannabinoids, delta(9)-tetrahydrocannabinol (delta(9)-THC) is presumed to be the cannabinoid primarily responsible for many marijuana-related effects, including increased food intake and subjective effects. Yet, there has been no systematic comparison of repeated doses of oral delta(9)-THC with repeated doses of smoked marijuana in the same individuals. To compare the effects of oral delta(9)-THC and smoked marijuana in humans under controlled laboratory conditions. Eleven healthy research volunteers, who reported smoking an average of six marijuana cigarettes per day, completed an 18-day residential study. Marijuana cigarettes (3.1% delta(9)-THC, q.i.d.) were smoked or delta(9)-THC (20 mg, q.i.d.) was taken orally using a staggered, double-blind, double-dummy procedure for three consecutive days. Four days of placebo administration separated each active drug condition. Psychomotor task performance, subjective effects, and food intake were measured throughout the day. Relative to placebo baseline, oral delta(9)-THC and smoked marijuana produced similar subjective-effect ratings (e.g., "high" and "mellow"), although some effects of smoked marijuana were more pronounced and less prone to the development of tolerance. Additionally, participants reported "negative" subjective effects (e.g., "irritable" and "miserable") during the days after smoking marijuana but not after oral delta(9)-THC. Both drugs increased food intake for 3 days of drug administration, but had little effect on psychomotor performance. These results indicate that the behavioral profile of effects of smoked marijuana (3.1% delta(9)-THC) is similar to the effects of oral delta(9)-THC (20 mg), with some subtle differences.
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Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.
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Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Delta-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Delta-9-THC has not been established. In a 3-day, double-blind, randomized, placebo-controlled study, the dose-related effects of 0, 2.5, and 5 mg intravenous Delta-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls. Delta-9-THC (1) produced transient psychotomimetic effects and perceptual alterations; (2) impaired memory and attention; (3) increased subjective effects of 'high'; (4) produced tachycardia; and (5) increased serum cortisol in both groups. However, relative to controls, frequent users showed blunted responses to the psychotomimetic, perceptual altering, cognitive impairing, anxiogenic, and cortisol increasing effects of Delta-9-THC but not to its euphoric effects. Frequent users also had lower prolactin levels. These data suggest that frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.
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Using a federally compatible, naturalistic at-home administration procedure, the present study examined the acute effects of three cannabis flower chemovars with different tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios, in order to test whether chemovars with a higher CBD content produce different effects. Participants were randomly assigned to ad libitum administration of one of three chemovars (THC-dominant: 24% THC, 1% CBD; THC+CBD: 9% THC, 10% CBD; CBD-dominant: 1% THC, 23% CBD); 159 regular cannabis users (male = 94, female = 65) were assessed in a mobile pharmacology lab before, immediately after, and 1 h after ad libitum administration of their assigned chemovar. Plasma cannabinoids as well as positive (e.g., high, elation) and negative (e.g., paranoia and anxiety) subjective effects were assessed at each time points. Participants who used the CBD-dominant and THC + CBD chemovars had significantly less THC and more CBD in plasma samples compared to participants who used the THC-dominant chemovar. Further, the THC + CBD chemovar was associated with similar levels of positive subjective effects, but significantly less paranoia and anxiety, as compared to the THC-dominant chemovar. This is one of the first studies to examine the differential effects of various THC to CBD ratios using chemovars that are widely available in state-regulated markets. Individuals using a THC + CBD chemovar had significantly lower plasma THC concentrations and reported less paranoia and anxiety while also reporting similar positive mood effects as compared to individuals using THC only, which is intriguing from a harm reduction perspective. Further research is needed to clarify the harm reduction potential of CBD in cannabis products.
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None: At least 100 cannabis species are compounds known as cannabinoids, a molecule with a 21-carbon terpenophenolic skeleton. Cannabinoids produce more than 100 naturally occurring chemicals, the most abundant of which are Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), terpenes, and flavonoids. THC and CBD bind with cannabinoid receptors (CB1 and CB2), which are present in the brain and many organs. Metabolism of cannabis is determined by the route of consumption. When inhaled, THC and its metabolites enter the bloodstream rapidly via the lungs; they achieve peak levels within 6 to 10 minutes and reach the brain and various organs. The bioavailability of inhaled THC is 10% to 35%. After THC is absorbed, it travels to the liver where most of it is eliminated or metabolized to 11-OH-THC or 11-COOH-THC. The remaining THC and its metabolites enter the circulation. The bioavailability of ingested THC is only 4% to 12%. THC is highly lipid soluble and is therefore rapidly taken up by fat tissue. The plasma half-life of THC is 1 to 3 days in occasional users and 5 to 13 days in chronic users. The bioavailability of CBD via inhalation is 11% to 45%, whereas that of oral CBD is 6%. CBD has high lipophilicity and therefore is rapidly distributed in the brain, adipose tissue, and other organs. CBD is hydroxylated to 7-OH-CBD and 7-COOH-CBD by cytochrome P450 enzymes CYP3A4 and CYP2C9 in the liver and is excreted mainly in feces and less in urine. The plasma half-life of CBD is 18 to 32 hours.
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Background Prior controlled cannabis research has mostly focused on smoked cannabis and predominantly included frequent cannabis users. Oral cannabis products (“edibles”) make up a large and growing segment of the retail cannabis market. This study sought to characterize the pharmacodynamic effects of oral cannabis among infrequent cannabis users. Methods Seventeen healthy adults who had not used cannabis for at least 90 days completed four experimental sessions in which they consumed a cannabis-infused brownie that contained 0, 10, 25, or 50 mg THC. Subjective effects, vital signs, cognitive/psychomotor performance, and blood THC concentrations were assessed before and for 8 hours after dosing. Results Relative to placebo, the 10 mg THC dose produced discriminable subjective drug effects and elevated heart rate but did not alter cognitive/psychomotor performance. The 25 and 50 mg THC doses elicited pronounced subjective effects and markedly impaired cognitive and psychomotor functioning compared with placebo. For all active doses, pharmacodynamic effects did not manifest until 30-60 minutes after ingestion, and peak effects occurred 1.5-3 hours post-administration. Blood THC levels were significantly correlated with some pharmacodynamic drug effects, but were substantially lower than what is typically observed after cannabis inhalation. Conclusion Ingestion of oral cannabis dose-dependently altered subjective drug effects and impaired cognitive performance. Unlike inhaled forms of cannabis for which acute effects occur almost immediately, effects of oral cannabis were considerably delayed. In an era of legalization, education about the time course of drug effects for cannabis edibles is needed to facilitate dose titration and reduce acute overdose incidents.
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The recent liberalisation of cannabis regulation has increased public and scientific debate about its potential benefits and risks. A key focus has been the extent to which cannabidiol (CBD) might influence the acute effects of delta-9-tetrahydrocannabinol (THC), but this has never been reviewed systematically. In this systematic review of how CBD influences the acute effects of THC we identified 16 studies involving 466 participants. Ten studies were judged at low risk of bias. The findings were mixed, although CBD was found to reduce the effects of THC in several studies. Some studies found that CBD reduced intense experiences of anxiety or psychosis-like effects of THC and blunted some of the impairments on emotion and reward processing. However, CBD did not consistently influence the effects of THC across all studies and outcomes. There was considerable heterogeneity in dose, route of administration and THC:CBD ratio across studies and no clear dose-response profile emerged. Although findings were mixed, this review suggests that CBD may interact with some acute effects of THC.
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Laws regulating cannabis have changed radically in the U.S. and abroad. Historically, users smoked dried cannabis flowers that contained Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, as the principal product constituent. Coincident with cannabis legalization and increased interest in medicinal use of the plant, there is now an expansive retail cannabis marketplace with novel cannabis products, formulations, and methods of administration. In this review, we describe emergent cannabis product chemotypes (e.g. THC-dominant, CBD-dominant, balanced or ‘hybrid’ with high concentrations of THC and CBD), product formulations (e.g. edibles, concentrates), and methods of administration (e.g. smoked, vaporized, orally ingested). Psychologists can play a pivotal role in studying the health impact of cannabis legalization and conducting research to inform product regulation.
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Background Although the rate of cannabis use by older adults is increasing more quickly than all other age groups, little is known about the reasons why older adults use cannabis and the outcomes they experience. Objective The objective of this study was to identify the most salient themes concerning the use of medical and recreational cannabis by older adults living in Colorado. Specifically, we sought to (1) characterize perceptions of cannabis use by users and non-users, (2) determine how older adults access cannabis, and (3) explicate both positive and negative outcomes associated with cannabis use. Methods Between June and November 2017, we conducted 17 focus groups in senior centers, health clinics, and cannabis dispensaries in 15 Colorado cities. Participants included 136 persons aged over 60 years who were both users and non-users of cannabis. We coded and analyzed session transcripts using thematic analysis with NVivo software. Results We identified 16 codes from which five main themes emerged. These themes included: a lack of education and research about cannabis, a lack of provider communication, access to medical cannabis, the outcomes of cannabis use, and a reluctance to discuss cannabis use. Conclusions Older adults want more information about cannabis and desire to communicate with their healthcare providers. Older adults who used cannabis for medical purposes reported positive outcomes but highlighted difficulties in accessing medical cannabis. Older adults in Colorado also revealed how a stigma continues to be attached to using cannabis.
Article
Background Studies suggest cannabis may improve symptoms like pain and muscle spasticity in patients with multiple sclerosis (PwMS). Despite cannabis’ new-found legality and availability, few studies have explored the profile of PwMS cannabis users and characteristics of their use, particularly in a state where cannabis is legal both for recreational and medicinal use. The purpose of the current study was to evaluate cannabis use among PwMS at a large academic multiple sclerosis (MS) clinic, specifically: (1) prevalence, (2) products used (e.g., cannabidiol vs Δ⁹-tetrahydocannabinol), (3) symptom treatment, and (4) patient characteristics. Methods PwMS completed questions assessing personal opinions about cannabis use, characteristics of cannabis use, MS history, and sociodemographic details, as well as the self-reported disability-Patient Determined Disease Steps (PDDS), overall quality of life-the Patient Reported Outcome Measure Information System (PROMIS-10), and cognition-the Neuro-QoL ACGC v1.0 measures. Results Thirty-eight percent (n = 96) of PwMS were current Cannabis users (CUs). Although there were no sociodemographic or clinical differences (p ≤ 0.05) between CUs and Non-Cannabis users (NUs), CUs had significantly higher median disability compared to NUs (PDDS = 2 vs. 1; p = 0.02). Among CUs, 57% categorized their use as strictly medicinal. CUs reported using cannabis most often for pain and insomnia/poor sleep and experienced greater than 60% benefit/relief from cannabis use. Over 90% of respondents desire more research on cannabis for MS, and 74% indicated they would consider using cannabis for their MS. Conclusion As cannabis legalization has impacted the variety of cannabis products available, there appears to be growing numbers of PwMS using cannabis, with this study's CUs reporting use of highly efficacious products with minimal side-effects.
Article
Background: There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Methods: Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Results: Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Conclusions: Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders.
Article
Background: Cannabis use is common, and associated with adverse health outcomes. 'Routes of administration' (ROAs) for cannabis use have increasingly diversified, in part influenced by developments towards legalization. This paper sought to review data on prevalence and health outcomes associated with different ROAs. Methods: This scoping review followed a structured approach. Electronic searches for English-language peer-reviewed publications were conducted in primary databases (i.e., MEDLINE, EMBASE, PsycINFO, Google Scholar) based on pertinent keywords. Studies were included if they contained information on prevalence and/or health outcomes related to cannabis use ROAs. Relevant data were screened, extracted and narratively summarized under distinct ROA categories. Results: Overall, there is a paucity of rigorous and high-quality data on health outcomes from cannabis ROAs, especially in direct and quantifiable comparison. Most data exist on smoking combusted cannabis, which is associated with various adverse respiratory system outcomes (e.g., bronchitis, lung function). Vaporizing natural cannabis and ingesting edibles appear to reduce respiratory system problems, but may come with other risks (e.g., delayed impairment, use 'normalization'). Vaporizing cannabis concentrates can result in distinct acute risks (e.g., excessive impairment, injuries). Other ROAs are uncommon and under-researched. Conclusions: ROAs appear to distinctly influence health outcomes from cannabis use, yet systematic data for comparative assessments are largely lacking; these evidence gaps require filling. Especially in emerging legalization regimes, ROAs should be subject to evidence-based regulation towards improved public health outcomes. Concretely, vaporizers and edibles may offer potential for reduced health risks, especially concerning respiratory problems. Adequate cannabis product regulation (e.g., purity, labeling, THC-restrictions) is required to complement ROA-based effects.
Article
Background: Edible marijuana products have become extremely popular in states that have legalized marijuana for recreational use. Objectives: The goal of this research was to provide a better understanding of consumer perceptions of edible marijuana products, including why they prefer edibles relative to other forms of marijuana (e.g., smoking) and their concerns regarding the consumption of edibles. Methods: We conducted eight focus groups (four groups in Denver, Colorado, and four groups in Seattle, Washington) in February 2016 with 62 adult consumers of edibles. Focus group transcripts were coded in QSR NVivo 10.0 qualitative analysis software, and coding reports identified trends across participants. Results: Most participants preferred edibles to smoking marijuana because there is no smell from smoke and no secondhand smoke. Other reasons participants like edibles included convenience, discreetness, longer-lasting highs, less intense highs, and edibles' ability to aid in relaxation and reduce anxiety more so than smoking marijuana. Concerns and dislikes about edibles included delayed effects, unexpected highs, the unpredictability of the high, and inconsistency of distribution of marijuana in the product. No participants in either location mentioned harmful health effects from consuming edibles as a concern. Conclusions/Importance: The present study was qualitative in nature and provides a good starting point for further research to quantify through surveys how consumers understand and use edibles. Such information will help guide policy makers and regulators as they establish regulations for edibles. Also, such research can help inform educational campaigns on proper use of edibles for recreational purposes.
Article
Background: Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmaco- and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. Methods: To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11OH-THC), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. Results: In contrast to atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI) was associated with extensive ion suppression in plasma and urine samples. Thus, the APCI assay was validated showing a lower limit of quantification (LLOQ) ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantitation (ULOQ) was 400 ng/mL except for THC-C-gluc with a ULOQ of 2000 ng/mL. The linearity was r> 0.99 for all analyzed calibration curves. Acceptance criteria for intra- and inter-batch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% inter-batch accuracy) and CBDV (inter-batch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intra-batch accuracy. Conclusions: This assay allows not only for monitoring THC and its major metabolites, but also of major cannabinoids that are of interest for marijuana research and clinical practice.
Article
This study analyzed the dose accuracy of labels from edibile medical cannabis products dispensed in 3 US cities. As the use of cannabis (marijuana) for medical purposes has expanded, a variety of edible products for oral consumption has been developed. An estimated 16% to 26% of patients using medical cannabis consume edible products.¹,2 Even though oral consumption lacks the harmful by-products of smoking, difficult dose titration can result in overdosing or underdosing, highlighting the importance of accurate product labeling.
Article
Findings for this article are derived from our National Institute on Drug Abuse (NIDA)-funded study of older and younger Baby Boomers and marijuana use. We explore Baby Boomers’ use of a variety of cannabis products and the motives behind the choices they make concerning these preparations. Cannabis concentrates and edible goods have become increasingly popular over the years. With so many new ways to consume marijuana and a growing number of medical marijuana dispensaries, more and more people are using alternative cannabis products to relieve physical ailments, to improve mental health issues, and for recreational purposes. We explore Baby Boomers’ motives to use and how aging may change those motives and influence their choices in cannabis delivery systems. As they get older, Boomers’ health concerns grow and many have turned to these alternative cannabis products to improve mental and physical well-being, and even to reduce the potential risks of traditional marijuana smoking.
Article
Rationale An increase in the potency of the cannabis cigarettes has been observed over the past three decades. Objectives In this study, we aimed to establish the impact of Δ9-tetrahydrocannabinol (THC) on the rating of subjective effects (intensity and duration of the effects), up to 23 % THC potency (69 mg THC) among recreational users. Methods Recreational users (N = 24) smoked cannabis cigarettes with four doses of THC (placebo 29, 49 and 69 mg of THC) on four separate test days in a randomized, double-blind, placebo-controlled, crossover study. The participants filled in three different questionnaires measuring subjective effects during the exposure up to 8 h post-smoking. The ‘high’ feeling, heart rate, blood pressure and THC serum concentrations were also regularly recorded during these 8 h. Results THC significantly increased the high feeling, dizziness, dry-mouthed feeling, palpitations, impaired memory and concentration, and ‘down’, ‘sedated’ and ‘anxious’ feelings. In addition, THC significantly decreased alertness, contentment and calmness. A cubic relationship was observed between ‘feeling the drug’ and ‘wanting more’. The THC-induced decrease in ‘feeling stimulated’ and increase in anxiety lasted up to 8 h post-smoking. Sedation at 8 h post-smoking was increased by a factor of 5.7 with the highest THC dose, compared to the placebo. Conclusions This study shows a strong effect of cannabis containing high percentages of THC on the rating of subjective effects. Regular users and forensic toxicologists should be aware that the THC-induced increase in ‘feeling sedated’ continues longer with a 69 mg THC dose than with a 29 mg THC dose.
Article
The reinforcing and subjective effects of oral delta-9-tetrahydrocannabinol (THC) and smoked marijuana were studied in two groups of regular marijuana users. One group (N=10) was tested with smoked marijuana and the other (N=11) with oral THC. Reinforcing effects were measured with a discrete-trial choice procedure which allowed subjects to choose between the self-administration of active drug or placebo on two independent occasions. Subjective effects and heart rate were measured before and after drug administration. Smoked active marijuana was chosen over placebo on both choice occasions by all subjects. Similarly, oral THC was chosen over placebo on both occasions by all but one subject. Both active drug treatments produced qualitatively and quantitatively similar subjective effects, and both significantly increased heart rate, although the time course of effects differed substantially between the two treatments. The results demonstrate that both smoked marijuana and oral THC can serve as positive reinforcers in human subjects under laboratory conditions. The experimental paradigm used here should prove useful for identifying factors that influence the self-administration of marijuana and other cannabinoids by humans.
Article
The present study investigated the correlation between cancer pain severity and mood states, and addressed methodological issues involved in measuring the association between these groups of variables. Five monthly interviews were administered to 95 cancer pain patients; each interview contained four measures of pain severity and the Profile of Mood States (POMS). The relationships between the two sets of variables were assessed using both interindividual (cross-sectional) and intraindividual (within-subject) methods of correlational analysis. Both types of analyses suggested small but significant positive correlations between the pain measures and negative mood states, and inverse correlations between pain and positive mood. The data also indicated that patients reported high levels of pain but reported little mood disturbance. In addressing methodological issues, the study clarified conceptual and computational differences between the two types of correlational analyses and indicated the appropriate applications of each method.
Article
The Alcohol Use Disorders Identification Test (AUDIT) has been developed from a six-country WHO collaborative project as a screening instrument for hazardous and harmful alcohol consumption. It is a 10-item questionnaire which covers the domains of alcohol consumption, drinking behaviour, and alcohol-related problems. Questions were selected from a 150-item assessment schedule (which was administered to 1888 persons attending representative primary health care facilities) on the basis of their representativeness for these conceptual domains and their perceived usefulness for intervention. Responses to each question are scored from 0 to 4, giving a maximum possible score of 40. Among those diagnosed as having hazardous or harmful alcohol use, 92% had an AUDIT score of 8 or more, and 94% of those with non-hazardous consumption had a score of less than 8. AUDIT provides a simple method of early detection of hazardous and harmful alcohol use in primary health care settings and is the first instrument of its type to be derived on the basis of a cross-national study.