Hot Dab Associated Pneumonitis - a case report.

BACKGROUND: Dabbing is recently getting popular among young adults. It is a new method of using the most active form of marijuana where large amounts of concentrated tetrahydrocannabinol are inhaled. Tetrahydrocannabinol is associated with a feeling of 'High' which makes the user feel joyous and relaxed. With increasing use of such techniques, dabbing becomes an important differential for evaluation of acute respiratory failure with pneumonitis especially in the adult population. CASE PRESENTATION: A Fifty-one years old Caucasian man presented to the hospital with chest pressure and shortness of breath. The patient was noted to be hypoxic, desaturating down to 82-83% on nasal cannula oxygen. Imaging revealed bilateral lung infiltrates. Patient was started on high flow oxygen, broad spectrum antibiotics and intravenous corticosteroids. The patient gradually improved and was able to come off oxygen completely. He was discharged home on prednisone taper. CONCLUSIONS: Dabbing is a newer technique which has been gaining popularity for marijuana usage. With the legalization of marijuana, newer techniques are getting popular. Our case report emphasizes the importance of keeping dabbing as a differential when a patient presents with respiratory failure and has concerns for pneumonitis. Patients might not reveal until specifically asked about their practices.

[Cannabis use and cannabis use disorders]. / Cannabiskonsum und Cannabiskonsumstörungen.

Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly.

Fetal Cannabinoid Syndrome: Behavioral and Brain Alterations of the Offspring Exposed to Dronabinol during Gestation and Lactation.

This study establishes a fetal cannabinoid syndrome model to evaluate the effects of high doses of dronabinol (synthetic THC) during pregnancy and lactation on behavioral and brain changes in male and female progeny and their susceptibility to alcohol consumption. Female C57BL/6J mice received dronabinol (10 mg/kg/12 h, p.o.) from gestational day 5 to postnatal day 21. On the weaning day, the offspring were separated by sex, and on postnatal day 60, behavioral and neurobiological changes were analyzed. Mice exposed to dronabinol exhibited increased anxiogenic and depressive-like behaviors and cognitive impairment. These behaviors were associated with neurodevelopment-related gene and protein expression changes, establishing, for the first time, an association among behavioral changes, cognitive impairment, and neurobiological alterations. Exposure to dronabinol during pregnancy and lactation disrupted the reward system, leading to increased motivation to consume alcohol in the offspring. All these modifications exhibited sex-dependent patterns. These findings reveal the pronounced adverse effects on fetal neurodevelopment resulting from cannabis use during pregnancy and lactation and strongly suggest the need to prevent mothers who use cannabis in this period from the severe and permanent side effects on behavior and brain development that may occur in their children.

Using Large Language Models to Support Content Analysis: A Case Study of ChatGPT for Adverse Event Detection.

This study explores the potential of using large language models to assist content analysis by conducting a case study to identify adverse events (AEs) in social media posts. The case study compares ChatGPT's performance with human annotators' in detecting AEs associated with delta-8-tetrahydrocannabinol, a cannabis-derived product. Using the identical instructions given to human annotators, ChatGPT closely approximated human results, with a high degree of agreement noted: 94.4% (9436/10,000) for any AE detection (Fleiss κ=0.95) and 99.3% (9931/10,000) for serious AEs (κ=0.96). These findings suggest that ChatGPT has the potential to replicate human annotation accurately and efficiently. The study recognizes possible limitations, including concerns about the generalizability due to ChatGPT's training data, and prompts further research with different models, data sources, and content analysis tasks. The study highlights the promise of large language models for enhancing the efficiency of biomedical research.

Evaluating possible 'next day' impairment in insomnia patients administered an oral medicinal cannabis product by night: a pilot randomized controlled trial.

Cannabis and its major constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo. This paper describes the secondary outcomes of a larger study investigating the effects of THC/CBD on insomnia disorder. Twenty adults [16 female; mean (SD) age, 46.1 (8.6) y] with physician-diagnosed insomnia who infrequently use cannabis completed two 24 h in-laboratory visits involving acute oral administration of combined 10 mg THC and 200 mg CBD ('THC/CBD') or placebo in a randomised, double-blind, crossover trial design. Outcome measures included 'next day' (≥9 h post-treatment) performance on cognitive and psychomotor function tasks, simulated driving performance, subjective drug effects, and mood. We found no differences in 'next day' performance on 27 out of 28 tests of cognitive and psychomotor function and simulated driving performance relative to placebo. THC/CBD produced a small decrease (-1.4%, p=.016, d=-0.6) in accuracy on the Stroop-Colour Task (easy/congruent) but not the Stroop-Word Task (hard/incongruent). THC/CBD also produced a small increase (+8.6, p=.042, d=0.3) in self-ratings of Sedated at 10 h post-treatment, but with no accompanying changes in subjective ratings of Alert or Sleepy (p's>0.05). In conclusion, we found a lack of notable 'next day' impairment to cognitive and psychomotor function and simulated driving performance following evening use of 10 mg oral THC, in combination with 200 mg CBD, in an insomnia population who infrequently use cannabis.

Efectos de la marihuana en la salud bucal / Effects of marijuana on oral health

Aun cuando las autoridades del Sector Salud en México no se han declarado respecto al uso medicinal de la marihuana, con el objetivo de conocer el estado actual internacional sobre sus riesgos y usos terapéuticos, investigamos los avances reportados en la actualidad, así como las comunidades que han despenalizado su uso. Se presenta su origen como elemento terapéutico, pueblos involucrados, diversas denominaciones, historicidad, las diversas preparaciones, farmacodinamia, sus efectos nocivos a la salud en general y particularmente en boca, sus posibles usos en odontología tomando en cuenta sus propiedades terapéuticas. ampliamente reseñadas en relación a otros lugares del organismo. Finalmente, la propuesta de investigación en odontología con especial énfasis en aquellas especialidades donde la inflamación y el dolor agudo estén presentes de manera significativa (AU)

Although health authorities in Mexico have not officially declared their stance on the medicinal use of marijuana, our research aims to explore the current international status regarding its risks and therapeutic uses. We have investigated the latest reported advancements and examined communities that have decriminalized its usage. This presentation encompasses its therapeutic origin, involved communities, various designations, historical context, diverse preparations, pharmacodynamics, its adverse effects on overall health and particularly oral health, as well as its potential applications in dentistry, considering its widely documented therapeutic properties in comparison to other areas of the body. Finally, our research proposal in dentistry places special emphasis on specialties where inflammation and acute pain are significantly present (AU)

Vaporized D-limonene selectively mitigates the acute anxiogenic effects of Δ9-tetrahydrocannabinol in healthy adults who intermittently use cannabis.

BACKGROUND: Cannabis contains hundreds of chemical constituents beyond delta-9-tetrahydrocannabinol (THC), which is believed to drive most of its acute pharmacodynamic effects. The entourage effect theory asserts that non-THC constituents can impact acute cannabis effects, but few empirical studies have systematically evaluated this theory in humans. This study assessed whether the cannabis terpenoid d-limonene mitigates the acute anxiogenic effects of THC. METHODS: Twenty healthy adults completed nine, double-blind outpatient sessions in which they inhaled vaporized THC alone (15mg or 30mg), d-limonene alone (1mg or 5mg), the same doses of THC and d-limonene together, or placebo; a subset of participants (n=12) completed a tenth session in which 30mg THC+15mg d-limonene was administered. Outcomes included subjective drug effects, cognitive/psychomotor performance, vital signs, and plasma THC and d-limonene concentrations. RESULTS: When d-limonene was administered alone, pharmacodynamic outcomes did not differ from placebo. Administration of 15mg and 30mg THC alone produced subjective, cognitive, and physiological effects typical of acute cannabis exposure. Ratings of anxiety-like subjective effects qualitatively decreased as d-limonene dose increased and concurrent administration of 30mg THC+15mg d-limonene significantly reduced ratings of "anxious/nervous" and "paranoid" compared with 30mg THC alone. Other pharmacodynamic effects were unchanged by d-limonene. D-limonene plasma concentrations were dose orderly, and concurrent administration of d-limonene did not alter THC pharmacokinetics. CONCLUSIONS: D-limonene selectively attenuated THC-induced anxiogenic effects, suggesting this terpenoid could increase the therapeutic index of THC. Future research should determine whether this effect extends to oral dose formulations and evaluate the interactions between other cannabis terpenoids or cannabinoids and THC.

Prenatal delta-9-tetrahydrocannabinol exposure alters fetal neurodevelopment in rhesus macaques.

Prenatal cannabis use is associated with adverse offspring neurodevelopmental outcomes, however the underlying mechanisms are relatively unknown. We sought to determine the impact of chronic delta-9-tetrahydrocannabinol (THC) exposure on fetal neurodevelopment in a rhesus macaque model using advanced imaging combined with molecular and tissue studies. Animals were divided into two groups, control (n = 5) and THC-exposed (n = 5), which received a daily THC edible pre-conception and throughout pregnancy. Fetal T2-weighted MRI was performed at gestational days 85 (G85), G110, G135 and G155 to assess volumetric brain development. At G155, animals underwent cesarean delivery with collection of fetal cerebrospinal fluid (CSF) for microRNA (miRNA) studies and fetal tissue for histologic analysis. THC exposure was associated with significant age by sex interactions in brain growth, and differences in fetal brain histology suggestive of brain dysregulation. Two extracellular vesicle associated-miRNAs were identified in THC-exposed fetal CSF; pathway analysis suggests that these miRNAs are associated with dysregulated axonal guidance and netrin signaling. This data is indicative of subtle molecular changes consistent with the observed histological data, suggesting a potential role for fetal miRNA regulation by THC. Further studies are needed to determine whether these adverse findings correlate with long-term offspring neurodevelopmental health.

Differences in prescribed medicinal cannabis use by cannabinoid product composition: Findings from the cannabis as medicine survey 2020 (CAMS-20) Australia-wide study.

INTRODUCTION: Prescribed medicinal cannabis (MC) is an increasingly common prescription in Australia for treating pain, anxiety, and sleep disorders. Prescribed MC products generally contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in a variety of dose levels and forms. It is unclear whether THC and CBD products are used by patients with different characteristics and for different conditions. OBJECTIVES: To examine consumer experiences of using THC- and CBD-containing prescribed MC products to better understand how they are being used within the Australian context. METHODS: We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-20 survey), consisting of Australian residents using cannabis for therapeutic reasons. We focused on a subgroup of participants (N = 546) receiving prescribed MC products. We utilised linear, logistic, and multinomial regression modelling to analyse responses to survey questions based on the cannabinoid profile of the prescribed product. RESULTS: Participants prescribed THC-dominant MC products were statistically more likely to be younger, male, and to prefer inhaled routes of administration than participants using CBD-dominant products who were older, female, and preferred oral routes of administration. Pain and mental health were the most common reasons for all types of prescribed MC, but were more likely to be treated with THC than CBD despite the significantly higher risk of mild to severe drowsiness, dry mouth and eye irritation. Consumer reported effectiveness of prescribed MC was very positive, particularly for THC-containing products. Consumers on opioids and antipsychotics were statistically more likely to be prescribed THC-containing products than products containing CBD only, despite the greater risk of impairment. CONCLUSIONS: This Australia-wide study found clear differences in consumer-reported experiences of prescribed THC- and CBD-containing products. Current prescriptions of these products do not always align with relevant clinical guidance. Educating prescribers around cannabinoid products is essential to ensure optimal prescribing practices and to prevent avoidable drug side effects and interactions.

Tolerability of High-Dose Oral Δ9-THC: Implications for Human Laboratory Study Design.

Background: Δ9-tetrahydrocannabinol (THC), the primary intoxicating compound in cannabis, has been tested extensively in controlled administration human studies. Some studies require a high THC dose that may induce adverse events (AEs), such as those testing novel treatments for cannabinoid overdose. Although there are ethical concerns related to administering high THC doses, there is no systematic analysis on studies utilizing these doses. In this review, we examine studies that administered oral THC doses ≥30 mg ("high-dose THC"), focusing on reported tolerability, subjective effects, and pharmacokinetics (PK), with the objective to inform the design of future studies. Methods: A comprehensive PubMed search was performed to identify studies meeting pre-specified criteria. Results: Our search identified 27 publications from 17 high-dose oral THC laboratory studies, with single doses up to 90 mg and multiple doses up to 210 mg per day. The maximum plasma THC concentration (Cmax) appeared to increase in a dose-proportional manner over this dose range. All high-dose THC studies enrolled participants with previous cannabis experience, although current use ranged from nonusers to regular cannabis users. High-dose THC was generally well tolerated with transient mild to moderate AE, including nausea and vomiting, anxiety, paranoia, and sedation. There were occasional participant withdrawals due to AEs, but there were no serious AE. Participants with frequent cannabis use tolerated high-dose THC best. Conclusion: Although based on limited data, THC was generally adequately tolerated with single oral doses of at least 50 mg in a controlled laboratory setting in healthy participants with past cannabis experience.

A Systematic Review of the Molecular and Cellular Alterations Induced by Cannabis That May Serve as Risk Factors for Bipolar Disorder.

BACKGROUND: Cannabis use is a risk factor of psychiatric illness, such as bipolar disorder type-I (BDI). Indeed, cannabis use strongly influences the onset and clinical course of BDI, although the biological mechanisms underlying this interaction remain unknown. Therefore, we have reviewed the biological mechanisms affected by cannabis use that may trigger BD. METHODS: A systematic review was carried out of articles in which gene expression was studied in cannabis users or human-derived cells exposed to tetrahydrocannabinol (THC) or cannabidiol (CBD). A second systematic review was then performed to identify articles in which gene expression was studied in BDI samples, highlighting those that described alterations to the same molecular and cellular mechanisms affected by cannabis/THC/CBD. RESULTS: The initial search identified 82 studies on cannabis and 962 on BDI. After removing duplicates and applying the inclusion/exclusion criteria, 9 studies into cannabis and 228 on BDI were retained. The molecular and cellular mechanisms altered by cannabis use or THC/CBD exposure were then identified, including neural development and function, cytoskeletal function, cell adhesion, mitochondrial biology, inflammatory related pathways, lipid metabolism, the endocannabinoid system, the hypocretin/orexin system, and apoptosis. Alterations to those activities were also described in 19 of 228 focused on BDI. CONCLUSIONS: The biological mechanisms described in this study may be good candidates to the search for diagnostic biomarkers and therapeutic targets for BDI. Because cannabis use can trigger the onset of BD, further studies would be of interest to determine whether they are involved in the early development of the disorder, prompting early treatment.

Somatic and anxiety-like behaviors in male and female rats during withdrawal from the non-selective cannabinoid agonist WIN 55,212-2.

Synthetic cannabinoids are associated with higher risk of dependence and more intense withdrawal symptoms than plant-derived Δ9-tetrahydrocannabinol (THC). Avoidance of withdrawal symptoms, including anxiogenic effects, can contribute to continued cannabinoid use. Adult male and female Long-Evans rats were given escalating doses of WIN 55,212-2 (WIN) via twice daily intrajugular infusions. Precipitated withdrawal was elicited with SR 141716 (rimonabant) 4 h after the final infusion. Global withdrawal scores (GWS) were compiled by summing z-scores of observed somatic behaviors over a 30-min period with locomotor activity simultaneously collected via beam breaks. Rimonabant precipitated withdrawal in female and male rats at 3 or 10 mg/kg, respectively, but the individual behaviors contributing to GWS were not identical. 3 mg/kg rimonabant did not impact locomotor behavior in females, but 10 mg/kg decreased locomotion in male controls. Spontaneous withdrawal observed between 6 and 96 h after the final infusion was quantifiable up to 24 h following WIN administration. Individual behaviors contributing to GWS varied by sex and time point. Males undergoing spontaneous withdrawal engaged in more locomotion than females undergoing withdrawal. Separate groups of rats were subjected to a battery of anxiety-like behavioral tests (elevated plus maze, open field test, and marble burying test) one or two weeks after WIN or vehicle infusions. At one week abstinence, sex-related effects were noted in marble burying and the open field test but were unrelated to drug treatment. At two weeks abstinence, females undergoing withdrawal spent more time grooming during marble burying and performed more marble manipulations than their male counterparts. WIN infusions did not impact estrous cycling, and GWS scores were not correlated with estrous at withdrawal. Collectively, these results show qualitative sex differences in behaviors contributing to the behavioral experience of cannabinoid withdrawal supporting clinical findings from THC.

Colorado drugged driving prevalence and impaired driving conviction rates: Effects of impaired driving definitions and a 5-nanogram limit for delta-9 tetrahydrocannabinol.

Objectives: How prevalent is drugged driving among Colorado drivers convicted of Driving Under the Influence (DUI)? What are the conviction rates of Colorado drivers charged with DUI, including impairment by marijuana's delta-9 tetrahydrocannabinol (THC)? Is Colorado's THC permissible inference law effective? To answer these questions, this report analyzes data published primarily in appendices of Colorado drugged driving reports.Methods: In 2017 Colorado began requiring annual analyses of Driving Under the Influence (DUI) offenses, including causes and judicial consequences of DUI offenses. These analyses are performed by the Division of Criminal Justice's Office of Research and Statistics (ORS) within the Department of Public Safety. Each analysis requires ORS to link toxicology and court data bases. Data linking enables reporting of charges and convictions by categories including alcohol only, THC only, and polydrug use (two or more drugs simultaneously). Reports have been published annually for 5 years, the latest published in 2023 which covers case filings for 2020.Results: A rough estimate of one-half of the state's DUI filings were attributed to drug use and half were attributed to alcohol only. The largest component of drugged driving was polydrug impairment, rather than impairment by a single drug like THC. Conviction rates in 2020 were 91% for alcohol only, 90% for polydrug cases, and 72% for THC only. Blood drug levels and law structure (per se, permissible inference, DUI definition) affected conviction rates significantly by defendant subsets. THC conviction rates in 2020 ranged from 11% to 100%, depending on blood drug levels and the legal charges.Conclusions: Efforts to educate the public about the dangers of drugged driving should emphasize polydrug impairment, not simply THC impairment. States should analyze data on causes and consequences of DUI arrests to understand what their drugged driving problems are and what they are not. Non-zero drug per se levels and defining DUI as "incapable of safe driving" can severely reduce the effectiveness of DUI laws.

Prenatal Exposure to Cannabis: Effects on Childhood Obesity and Cardiometabolic Health.

PURPOSE OF REVIEW: To consolidate information on the obesogenic and cardiometabolic effects of prenatal exposure to cannabis. RECENT FINDINGS: A PubMed search strategy updated from January 1, 2014, through 14 June 2023, produced a total of 47 epidemiologic studies and 12 animal studies. Prenatal exposure to cannabis is consistently associated with small for gestational age and low birth weight. After birth, these offspring gain weight rapidly and have increased adiposity and higher glucose (fat mass percentage) in childhood. More preclinical and prospective studies are needed to deepen our understanding of whether these associations vary by sex, dose, timing, and composition of cannabis (e.g., ratio of delta-Δ9-tetrahydrocannabinol [Δ9-THC] to cannabidiol [CBD]). Addressing these gaps may help to solidify causality and identify intervention strategies. Based on the available data, clinicians and public health officials should continue to caution against cannabis use during pregnancy to limit its potential obesogenic and adverse cardiometabolic effects on the offspring.

E-cigarette use-associated lung injury (EVALI).

The prevalence of vaping has overtaken conventional cigarettes as the most frequent form of nicotine consumption among 15-24-year olds. There are currently a large number of both legitimate and illegitimate products and suppliers offering more than 8000 different flavors of vape on the market, whose additives are not tested, studied or regulated and whose safety and toxicity profile remains unknown. In vitro studies have demonstrated a dose-dependent decrease in the viability of normal human bronchial epithelial cells after exposure to vapor from electronic vape devices.Short- and medium-term studies to date indicate that vapor-induced pulmonary lesions are the most serious and commonly reported side effect; such lesions include bilateral ground glass opacities in lung bases with subpleural preservation, bilateral infiltrates, pleural effusion, pneumomediastinum and nodular opacities. Cases of EVALI have been described in patients with daily exposure, as well as in users who reported having been exposed to these substances at least once a month. The most frequently inhaled substances are THC, flavored liquids of unknown content, and nicotine.The clinical manifestations of dyspnea and cough are the most frequent respiratory symptomatology, in addition to constitutional manifestations such as fever and chills, and gastrointestinal manifestations such as vomiting, nausea, abdominal pain and diarrhea. To these can be added the presence of tachypnea, tachycardia, elevated blood pressure, hypoxia, leukocytosis with neutrophilia and elevated ESR.

Cannabidiol does not attenuate acute delta-9-tetrahydrocannabinol-induced attentional bias in healthy volunteers: A randomised, double-blind, cross-over study.

AIMS: To test how attentional bias and explicit liking are influenced by delta-9-tetrahydrocannabinol (THC) and whether these effects are moderated by cannabidiol (CBD). DESIGN: Double-blind, randomised, within-subjects cross-over study. SETTING: NIHR Wellcome Trust Clinical Research Facility at King's College Hospital, London, United Kingdom. PARTICIPANTS/CASES: Forty-six infrequent cannabis users (cannabis use <1 per week). INTERVENTION(S): Across four sessions, participants inhaled vaporised cannabis containing 10 mg of THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1) or 30 mg (3:1) of CBD, administered in a randomised order and counter-balanced across participants (a total of 24 order groups). MEASUREMENTS: Participants completed two tasks: (1) Attentional Bias (AB), comparing reaction times toward visual probes presented behind 28 target stimuli (cannabis/food) compared with probes behind corresponding non-target (neutral) stimuli. Participants responding more quickly to probes behind target than non-target stimuli would indicate greater attentional bias to cannabis/food; (2) Picture Rating (PR), where all AB stimuli were rated on a 7-point pleasantness scale, measuring explicit liking. FINDINGS: During the AB task, participants were more biased toward cannabis stimuli in the 0:1 condition compared with baseline (mean difference = 12.2, 95% confidence intervals [CIs] = 1.20-23.3, d = 0.41, P = 0.03). No other significant AB or PR differences were found between cannabis and food stimuli between baseline and 0:1 condition (P > 0.05). No significant CBD effect was found on AB or PR task performance at any dose (P > 0.05). There was additionally no cumulative effect of THC exposure on AB or PR outcomes (P > 0.05). CONCLUSIONS: A double-blind, randomised, cross-over study among infrequent cannabis users found that inhaled delta-9-tetrahydrocannabinol increased attentional bias toward cannabis in the absence of explicit liking, a marker of liability toward cannabis use disorder. At the concentrations normally found in legal and illegal cannabis, cannabidiol had no influence on this effect.

Pharmacokinetics and pharmacodynamics of cannabis-based medicine in a patient population included in a randomized, placebo-controlled, clinical trial.

Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis-based medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, double-blinded, placebo-controlled, trial, 23 patients with MS (17 female) mean age 52 years (range 21-67) were enrolled in this substudy. They received oral capsules containing Δ9 -tetrahydrocannabinol (THC, n = 4), cannabidiol (CBD, n = 6), a combination (THC&CBD, n = 4), or placebo (n = 9). Maximum doses were 22.5 mg (THC) and 45 mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra-high-performance liquid chromatography-tandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5 mg) were Cmax 1.21 ng/mL, Tmax 2.68 h, and half-life 2.75 h, and for CBD (10 mg) were Cmax 2.67 ng/mL, Tmax 0.10 h, and half-life 4.95 h, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group.