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“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

* Address correspondence to: Frederick S. Barrett, PhD, Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, E-mail: [email protected]

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis.

Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A.

Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM.

Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse event needs to be considered in the clinical use of cannabis.

Introduction

Cannabis, containing the psychoactive constituent Δ-9 tetrahydrocannabinol (THC), was historically classified as a hallucinogen, possibly due to the observation of powerful psychoactive effects. Early case reports that documented the subjective effects of cannabis 1,2 included experiences of anxiety, physiological distress, spiritual or mystical effects, and alterations to perception, awareness, and insight. These case reports provided support for characterizing cannabis as a hallucinogen. 2 Currently, it is uncommon for cannabis to be categorized as a hallucinogen, but, as policy changes regarding the medicinal and nonmedicinal (i.e., “recreational”) use of cannabis are rapidly being implemented, revisiting this potential effect of cannabis is warranted.

Hallucinations may be elicited by a variety of psychoactive drugs, with variable pharmacology. That said, hallucinations are consistently observed, and, arguably, the defining feature of a subset of drugs. The primary subjective effects of classic hallucinogens (e.g., psilocybin, lysergic acid diethylamide, and dimethyltryptamine [DMT]) are altered perception and cognition, 3 mystical or spiritual experiences, 4,5 and occasional anxiety and physiological distress, 6 and the molecular mechanism of action of hallucinogens is understood to be 5HT2A receptor agonism. 7,8 A set of pharmacologically diverse atypical hallucinogens, including κ-opioid agonists (e.g., salvinorin A) 9 and N-methyl-D-aspartate (NMDA) antagonists (including ketamine and dextromethorphan [DXM]), 10 are also known to consistently produce effects similar to, but distinguishable from, those of classic hallucinogens. THC is a partial agonist of cannabinoid receptor type-1 (CB1) and type-2 (CB2) receptors. Neither THC, nor minor cannabinoids, nor the terpenoids present in cannabis plant material have known direct effects at the 5HT2A, κ-opioid, or NMDA receptor. 11

Most case reports describing hallucinations following acute cannabis exposure involve individuals with current psychosis or a family history of psychosis, populations that are known to have an atypical response to cannabis. 12 A growing literature continues to explore the relationship between cannabis use and development of psychosis among individuals with an underlying vulnerability for psychosis. 13–16 While perceptual alterations in healthy individuals during the acute effects of THC have been described, 17,18 empirical reports describing hallucinogen-like effects of cannabis and cannabis constituents in controlled settings and in healthy participants without a family history of psychosis are quite rare.

Peer-reviewed reports that do detail hallucinogen-like experiences in healthy adults predominantly come from research studies involving the administration of purified THC 16 or case reports of individuals who experience adverse reactions following use of synthetic cannabinoids (often full CB1 agonists with greater potency than THC), 19 rather than whole plant cannabis. This distinction is worth noting as it points to exogenous CB1 receptor agonism as a potential mechanism for inducing hallucinations, and also because it has been postulated that phytocannabinoids such as cannabidiol (CBD) 20 or terpenoids 11 that are present in the cannabis plant may mitigate some of the deleterious effects of THC.

The following report presents the case of an atypical response to cannabis that included self-reported “hallucinogen-like” effects after inhalation of vaporized cannabis containing THC, but nominal levels of CBD in a controlled laboratory study. To qualitatively investigate the phenomenology of this hallucinogen-like experience, we conducted cross-sectional comparisons of data from this case with archival data obtained from controlled behavioral pharmacology studies of cannabis, the classic hallucinogen psilocybin, and the atypical hallucinogens DXM and salvinorin A.

Methods

Approach

In the context of a double-blind, placebo-controlled laboratory study investigating the effects of smoked and vaporized cannabis, we present the details of an adverse reaction to inhalation of vaporized cannabis containing 25 mg THC (the “case dose”) in a healthy male research participant (H.C.). Ratings of subjective drug effects provided by H.C. during the case dose are compared with subjective data obtained from other participants in the same study, as well as subjective effects reported by participants in separate self-administration studies that evaluated acute dose effects of oral cannabis, psilocybin, 5 DXM, 10 and salvinorin A. 9,21

Study methods

All research studies were conducted at the Johns Hopkins Behavioral Pharmacology Research Unit (BPRU). Across investigations, research participants were enrolled if they were medically healthy adults who screened negative for current Axis I psychiatric disorders, denied a personal or family history of psychosis (i.e., first or second-degree relative), did not meet formal diagnostic criteria for substance use disorders (other than caffeine or tobacco), and were not taking medications that could interact with study drugs. Urine drug tests verified abstinence from drugs of abuse before all experimental sessions.

Cannabis studies

Subjective effects data from 31 healthy adult participants were collected across two cannabis self-administration studies; one experiment (N=17) evaluated acute doses of orally ingested cannabis in brownies that contained 0, 10, 25, and 50 mg THC, and a second study (N=14), in which H.C. was a participant, examined acute doses of smoked, and vaporized cannabis containing 0, 10, or 25 mg THC. Cannabis plant matter was sourced from and certified by the Drug Supply Program of the National Institute on Drug Abuse (NIDA) to contain 13.4% THC and 0.03% CBD. Dried cannabis was weighed and dispensed in a quantity that was calculated to contain the target dose of THC (e.g., 186.6 mg of cannabis would be vaporized to deliver 25 mg THC). Participants endorsed a history of cannabis use and denied use of cannabis for at least 30 days before study enrollment. Participants were not dependent on or seeking treatment for cannabis or other psychoactive drugs. A minimum of 1 week separated each dose condition to allow for a full washout of doses, and washout was biochemically verified with quantitative urine and blood toxicology tests.

Psilocybin study

Eighteen healthy adult participants, 17 who were hallucinogen-naive, completed five experimental sessions involving administration of 0, 5, 10, 20, and 30 mg/70 kg psilocybin doses in a controlled and supportive laboratory setting. 5 Drug administration sessions were separated by ∼1 month. Data collected during the 5 mg/70 kg dose is not included in this report.

DXM study

Twelve healthy adults with histories of hallucinogen use were administered up to eight doses of DXM (100–800 mg/70 kg), two doses of the sedative–hypnotic drug triazolam (0.25 and 0.5 mg/70 kg), and placebo under blinded conditions using an ascending dose run-up design. 10 A minimum of 48 h separated each drug administration session. All participants received at least the first four doses of DXM (100, 200, 300, and 400 mg/70 kg), but the study was halted before the 800 mg/70 kg dose for 10 participants due to adverse effects at lower doses. For the current comparison, we present data from placebo, 200 mg, the second highest (penultimate) dose, and the maximum dose administered to each participant.

Salvinorin A study

Eight healthy adults with previous lifetime use of a classic hallucinogen and at least one instance of salvia divinorum use in the past 5 years inhaled up to 16 ascending doses of vaporized salvinorin A (0.375–21 μg/kg). 9 A minimum of 24 h separated each drug administration session. Data from placebo, 9, 15, and 19.5 μg/kg doses were used for comparison in this study, as these doses of salvinorin A roughly corresponded to low, moderate, and high doses of psilocybin 5 on ratings of drug effect intensity.

Hallucinogen effects assessment

Participants across studies completed the Hallucinogen Rating Scale (HRS). 22 The HRS has been widely used to investigate the effects of a range of classic hallucinogens, including DMT, 23–26 psilocybin, 4,5 2C-B, 27 and 3,4-methylenedioxy-N-ethylamphetamine. 28 The HRS contains 59 items that are rated using a 5-point scale (0—not at all, 1—slightly, 2—moderately, 3—very much, 4—extremely) and scored with subscales indicating the degree of change that occurs during an acute drug experience from a more typical everyday experience across six dimensions (with example items for each dimension): Intensity (“high,” “a rush”), Somaesthesia (“change in body temperature,” “electric/tingling feeling”), Affect (“panic,” “euphoria”), Perception (“change in distinctiveness of sounds,” “change in brightness of objects in room”), Cognition (“change in rate of thinking,” “change in quality of thinking”), and Volition (“in control,” “able to move around if asked to”). Subscale scores were calculated as the average rating on all items that load onto each subscale.

Analyses

Average scores from the HRS were computed for each drug condition in each study, and plotted along with the HRS scores from responses for each dose and route of administration reported by H.C. A one-sample Student’s t-test was used to compare HRS scores from each drug condition in each study to the HRS scores for H.C. during the experimental session (vaporized cannabis containing 25 mg THC) in which he self-reported experiencing hallucinations.

Results

Case description

H.C. presented as a medically and psychiatrically healthy 30-year-old Caucasian male. He denied a history of significant health and psychiatric conditions and denied a family history of psychosis. He endorsed prior cannabis use, denied a history of any significant adverse effects associated with prior use, and he disclosed that 6 years had passed since he last used cannabis. He reported weekly use of alcohol and caffeine and denied use of nicotine/tobacco products and illicit drugs. He endorsed use of over-the-counter medication as needed for seasonal allergies. During the first three study sessions, he smoked cannabis that contained 0, 10, or 25 mg THC through hand-held pipe. Dose-related subjective drug effects, cardiovascular effects, and impairment on cognitive performance assessments were observed as expected. On the fourth experimental session (as with other experimental sessions), baseline assessments were within normal limits and urine drug screening (for common drugs of abuse) and breath alcohol tests were negative. After consuming a standard low-fat breakfast, the participant self-administered vaporized cannabis that contained 25 mg THC within 10 min (per protocol). Acute drug effects escalated in magnitude for the first 20 min following inhalation. He had difficulty responding to staff inquiries, was unable to complete self-report questionnaires, had difficulty keeping his head up, and appeared to periodically fall asleep or lose consciousness despite encouragement by research staff to stay awake and continue. He was unable to maintain a balanced, steady gait when he walked.

H.C. displayed behavior consistent with heavy sedation. The volunteer had difficulty maintaining consciousness and, at times, would not respond to verbal inquiries by study staff. He was under direct supervision of medical staff and neither his vital signs nor his behavior required medical intervention. He was able to complete a self-reported drug effect questionnaire, but had extreme difficulty completing cognitive performance assessments in the first 90 min following drug exposure. When he did speak, he reported feeling faint, dizzy, nauseated and that he was experiencing tingling sensations in his arms and legs and pain at the base of his neck.

Quantitative analysis (LC/MS/MS) of whole blood collected 10 min after the completion of cannabis administration (peak level measured in this study) showed 16 ng/mL THC, 3 ng/mL 11-OH-THC, and 17 ng/mL THC-COOH for H.C. These are consistent with mean values (14 ng/mL THC, 2 ng/mL 11-OH-THC, and 7 ng/mL THC-COOH) observed for all participants in this study at that time point and dose of vaporized cannabis. 29 Analysis of whole blood collected 10 min after the completion of cannabis administration in the smoked condition for the same dose level for H.C. (25 mg THC) showed 1 ng/mL THC, 1 ng/mL 11-OH-THC, and 4 ng/mL THC-COOH, and these values are consistent with mean values observed for all participants in this study at that time point and dose of smoked cannabis. 29

Three hours after drug administration, his symptoms began to decrease in severity. He indicated that he had experienced a dissociative state and altered perceptions of auditory and visual stimuli at the time of peak drug effect. He reported a hypersensitivity to voices at that time, which he described as if he was more aware of conversations around him, but was unable to hear or understand distinct words. He described visual distortions in the form of the environment and floor sinking away and the appearance of patterns moving on the carpet and chairs in the room. Additionally, he reported an “out-of-body” experience characterized by the feeling of being removed from his body, existing above it in space, and feeling that his surroundings were sinking away from him, which was also accompanied by a feeling of paralysis. He reported having had a similar experience when administered ketamine before surgery for a broken leg. Four hours after drug administration, and after eating lunch, H.C.’s symptoms of nausea, faintness, dissociation, and auditory, visual, and perceptual alterations had almost completely subsided. Five hours after drug administration, he appeared more alert and was able to complete all study-related tasks.

At the end of the experimental session, H.C. was prompted to recount his experience. He reported feeling overwhelmed that it was an uncomfortable, scary, and unpleasant experience akin to what he would expect an overdose or anxiety attack may feel like, and he indicated he never wanted to have the experience again. He expressed the sense that he thought he would “never come out of this” and that he would always feel the adverse effects. Within 8 h of acute drug administration, measures of cognitive performance, subjective mood and drug effects assessments, and vital signs had returned to baseline levels. The study medical team determined that there was no significant health risk with continued study participation and H.C. completed two remaining experimental sessions (lower dose and placebo cannabis) without significant discomfort.

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Comparison of Hallucinogen Rating Scale scores

Comparison of HRS scores across studies. (A) HRS Intensity score, (B) HRS Somaesthesia score, (C) HRS affect score, (D) HRS perception score, (E) HRS cognition score, and (F) HRS volition score. Each (A–F) compares the scores for the indicated scale of the HRS (ordinate) at each of four dose conditions for each drug (abscissa) for each of the studies identified within the legend. Pen=average of ratings provided after the second-highest (penultimate) dose of DXM that a given participant received. 10 Max=average of ratings provided after the highest dose of DXM that a given participant received. 10 “Cannabis THC dose” refers to the amount of THC contained in dried cannabis that was administered. Smoked cannabis and vaporized cannabis studies are not yet published. HRS, Hallucinogen Rating Scale; THC, tetrahydrocannabinol.

Discussion

The legalization of cannabis for medicinal and nonmedicinal use is rapidly expanding. The development of novel routes of administration and technologies for delivering cannabis raises concerns about the adequacy of available data to inform dosing recommendations and complete disclosure of potential adverse consequences. In a controlled research study, a 30-year-old healthy male research participant (H.C.) experienced an adverse reaction to an acute dose of vaporized cannabis containing 25 mg of THC self-administered over the course of 10 min. H.C.’s response appeared somewhat remarkable in that he reported distortions in visual and auditory perception, cognition, and volition. These effects are not typical in controlled laboratory studies of healthy adults who do not report prior adverse reactions to cannabis or family history of psychosis. He reported large changes on the Intensity, Somaesthesia, Perception, and Volition subscales of the HRS, domains associated with classical hallucinogen drug effects, but relatively low ratings on the Affect and Cognition subscales compared with HRS ratings obtained in controlled laboratory studies of other hallucinogenic drugs. The case dose was greater in Intensity and Perception subscales of the HRS compared with mean scores obtained following administration of high doses of psilocybin and salvinorin A, but was comparable to Perception scores following the maximum tolerated dose of DXM. 10 This is consistent with the participant’s report of a ketamine-like experience, given that DXM is a dissociative hallucinogen/anesthetic with a similar mechanism of action to ketamine (NMDA antagonism). The participant’s scores on the Somaesthesia subscale were similar to those observed after administration of a high dose of oral psilocybin (30 mg/70 kg), 5 both of which were greater than scores observed following DXM and salvinorin A administration. Scores on the Affect and Cognition subscales of the HRS for the case dose were low, consistent with scores provided by other participants in acute cannabis dosing studies, and were not consistent with the most intense reported experiences with psilocybin, DXM, or salvinorin A.

Given that changes in affect and cognition are core features of experience with classic hallucinogens, 3 it is difficult to attribute the reported case as an experience similar to that of a true classic hallucinogen. Curiously, Intensity scores for the case dose were equal to the Intensity score for H.C. after self-administration of smoked cannabis containing the 25 mg THC dose. H.C. did not report any hallucinations during the 25 mg THC smoked cannabis session. Also, scores on the Volition subscale for all vaporized drug conditions, including placebo, were greater than for sessions involving smoked cannabis for H.C., and were higher than those observed in archival study comparisons.

A number of case reports have been recently published that indicate psychotic or hallucinogen-like effects after ingestion of synthetic cannabinoids in both adults 19,30,31 and adolescents. 32,33 In many cases, these individuals, like H.C., were otherwise healthy, had negative toxicology screens for other substances of abuse, and were typically free of personal or family history of psychosis. 31 Unlike H.C., cases reported after consumption of synthetic cannabinoids included seizures, agitation or violent behavior, and frank psychosis, 19 or psychiatric syndromes persisting for days or longer after consumption of synthetic cannabinoids. 31 One study reported development of hallucinogen persistent perceptual disorder (HPPD) after synthetic cannabinoid use in otherwise healthy adults who had no prior history of natural or synthetic hallucinogen use 30 ; however, H.C. encountered no persisting effects, either HPPD or other, which were related to the case dose in this report. While THC is a partial agonist of the CB1 receptor, synthetic cannabinoids tend to be full CB1 agonists with high potency and high affinity for the CB1 receptor. These factors may contribute to a greater likelihood (compared with cannabis) of negative and hallucinogen-like effects after consumption of synthetic cannabinoids, and may suggest that CB1 agonism may underlie hallucinogen-like effects of cannabinoids. 34 While H.C.’s experience was atypical for a response to cannabis or THC, it does not seem that his experience is consistent with published case reports of “hallucinogenic” effects following consumption of synthetic cannabinoids.

Although the subjective effects that H.C. reported exhibited some similarities to the effects of classic and atypical hallucinogens ( Fig. 1 ), the overall profile of subjective effects as characterized by the HRS indicates that his experience was not wholly consistent with what would be expected for a classic hallucinogen, an NMDA antagonist dissociative hallucinogen (DXM, similar in effects to ketamine), or κ-opioid agonist (salvinorin A). Thus, it appears that the hallucinatory effects of cannabis, taken as a whole, may be qualitatively different than those of other hallucinogens, which suggests that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action.

Potential mechanisms of hallucinatory effects of cannabis

Although cannabis constituents do not have high affinity for direct pharmacological effects at 5HT2A, NMDA, or κ-opioid receptors, they may interact with the serotonin and glutamatergic systems. Multiple preclinical studies have demonstrated an impact of exogenous cannabinoid administration on 5-HT receptor expression and function3. CBD has been shown to alter psychological response to ketamine, 35 and subchronic administration of PCP (an NMDA antagonist) has been shown to change the effects of exogenous cannabinoids on prefrontal brain function. 36 However, existing studies suggest that the administration of exogenous cannabinoids does not modulate the κ-opioid receptor system. 37–39 While speculative, it is possible that hallucinatory effects of cannabinoids may be due to effects of exogenous cannabinoid on 5-HT or NMDA receptors; however, studies explicitly evaluating cannabinoid effects in brain areas associated with hallucinations are lacking.

Potential factors contributing to individual differences in cannabinoid response

Blood cannabinoid levels measured after the case dose were comparable to means observed in other study participants for vaporized administration of cannabis containing the same dose of THC (25 mg). Similarly, blood cannabinoid levels measured for H.C. after smoked administration of cannabis containing a dose of THC equal to the case dose were far lower than those measured after the case dose, consistent with means observed in other study participants. This is consistent with suggests that H.C. was not exposed to a greater amount of THC than other study participants. Given H.C.’s history of a strong reaction to a psychoactive and potentially hallucinogenic drug (ketamine) in a clinical setting, this suggests that H.C. may possess some unique sensitivity to psychoactive drugs.

Additional research is needed to help understand the neurobiological underpinnings of hallucinations that are sometimes occasioned following high-dose cannabis administration. For example, there may be genetic differences between individuals who experience and those who do not experience rare and atypical effects of cannabinoids that account for these effects. Although we did not sample and cannot address the genetic profile of H.C., it is possible that genes implicated in cannabis-induced psychosis (such as the DRD2, BDNF, AKT1, and COMT genes) 40 are also involved in the type and degree of experience that was encountered in this case. In addition, individual differences in sensitivity to CB1 agonists (potentially mediated by the CNR1 gene) may predict individual differences in response to exogenous cannabinoids. As mentioned previously, there are hypotheses that cannabis constituents other than THC (e.g., CBD, other phytocannabinoids, or terpenoids) may mitigate some of the adverse effects of THC. The cannabis used in the present study contained a high concentration of THC (13%) and low concentrations of CBD (<1%) and CBN (<1%). While an extreme ratio of THC to these minor phytocannabinoids may increase the likelihood of adverse events such as the hallucinations observed in this report, there is insufficient empirical data on the interaction between THC and other constituents of the plant to confidently draw that conclusion at this point. It is also important to note that most research evaluating the cannabinoid profile of commercial cannabis and related products indicate that very high THC and very low CBD products are predominant in the current retail market. 41–43

Limitations

The current report describes perceptual alterations and dissociative symptoms of a type that have been sparsely described previously as resulting from acute cannabis exposure. There is a substantial literature pointing to cannabinoid-induced psychosis in those with a personal or family history of psychosis. This particular susceptibility to psychosis was nominally ruled out in the case of H.C. in the medical and psychiatric history collected during screening, but the participant may have misreported or there may be a latent family history of which he was unaware. The current article is also limited in that cross-study comparisons with respect to the qualitative and quantitative characteristics of hallucinations across drug types was conducted with archival data across subjects rather than prospective evaluation within the same individuals. Additional research on the comparative effects of these drugs, especially those that incorporate genetic and neuroimaging components, is needed to extend the present observations.

Conclusion

In this article, we highlighted a rare but clinically significant response to acute cannabis dosing. The participant was functionally incapacitated for about 90 min and experienced strongly aversive and disorienting effects. It is unclear how frequently this type of reaction occurs in healthy adults without a family history of psychosis. H.C. did not have any health screening information that would have predicted this effect, indicating that this type of reaction should be considered in decision making regarding cannabis use. This case also demonstrates the importance of considering dose and route of administration in decision making regarding cannabis use as this individual did not exhibit similar effects at lower vaporized doses or smoking the same dose of cannabis.

Abbreviations Used

BPRU Behavioral Pharmacology Research Unit
CB1 cannabinoid receptor type-1
CBD cannabidiol
DMT dimethyltryptamine
DXM dextromethorphan
HPPD hallucinogen persistent perceptual disorder
HRS Hallucinogen Rating Scale
NIDA National Institute on Drug Abuse
NMDA N-methyl-D-aspartate
THC tetrahydrocannabinol

Acknowledgments

The research described here was funded by research contracts from the Substance Abuse and Mental Health Services Administration (SAMHSA; cannabis studies), National Institute on Drug Abuse (NIDA) grants R01-DA003889 (DXM and salvinorin A studies) and R01-DA-19151 (salvinorin A study), and grants from the Heffter Research Institute, the Betsy Gordon Foundation, and the Council on Spiritual Practices (psilocybin study). In addition, N.J.S. received salary support from NIDA postdoctoral training grant T32-DA07209, and F.S.B. was partially supported by NIH grant R03DA042336. The authors also thank the individuals at the NIDA Drug Supply Program for their support in conducting this research.

Author Disclosure Statement

Dr. Vandrey has received consulting fees or honoraria from Zynerba Pharmaceuticals, Insys Therapeutics, Battelle Memorial Institute, and several small businesses that cultivate, process, and/or dispense cannabis under state medical cannabis access programs. All other authors have no conflicts of interest to report.

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References

Cite this article as: Barrett FS, Schlienz NJ, Lembeck N, Waqas M, Vandrey R (2018) “Hallucinations” following acute cannabis dosing: a case report and comparison to other hallucinogenic drugs, Cannabis and Cannabinoid Research 3:1, 85–93, DOI: 10.1089/can.2017.0052.

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Those menstrual cramps cbd gummies guys are simply not human, If we cbd gummies hallucinations royal cbd gummies stay, we will not let us be cannon fodder! We are all following you.

Li Jiancheng didn t sneer this time, Although he didn t like Asda, the reason must be because of interests, but if the Li family no longer existed, what use would these interests be.

Wanwan can only stand here blankly, royal cbd like a cargo, waiting for their transaction, Seeing the embarrassed appearance cbd gummies hallucinations of everyone, Wang Li also showed a hint of pride.

When you become a big brother, you martha stewart cbd gummies in canada won t have your tail lifted to the sky.

When Mei heard this, she couldn t are cbd gummies legal in tennessee help laughing: Yes, son, I just don t know how those guys are doing.

At this moment, the nervousness also unfolded, I am also puzzled. If there is a collision on the frontal cbd gummies hallucinations battlefield, they must have no chance of winning, and they are all experts in the rivers and lakes, and their ability to fight alone is terrifying.

I also ask His Royal Highness to forgive me, My father should have cbd gummies hallucinations come botanical farms cbd gummies gummies cost to the door to thank him, but since my father took the Immortal Pill, all the dirt on his body has https://en.wikipedia.org/wiki/Cannabis_(drug) been discharged.

After a cbd 30 50mg gummies while, the rooster fell down! The sudden change made the shadow guards on the side Cbd Gummies Hallucinations tremble, this, this medicine pill lloyds pharmacy gummies delicious is poisonous.

Even Wang Li s father, Wang Ben, would not speak in such a tone, and top cbd oil only Wang Jian in the entire Wang family had the right to speak, But this is cbd gummies hallucinations clearly not the case now, Instead, he became cautious.

It wasn t just Wang Tong who came all the way, there cbd gummies with thc for sale were dozens of people around him.

These people are all military exploits to them, After returning, they delicious gummies cbd gummies hallucinations san francisco cbd gummies hallucinations top cbd oils in san clemente ca will be promoted Cbd Gummies Hallucinations and rich.

Hearing this, Gao Yao was immediately stunned, and now he just doesn t know what to do online shop cbd for anxiety in gummies mg his head. Only cbd gummies over the counter gummies products hallucinations when the empire is stable can they be relieved of their armies and return to their fields, and they can live Cbd Gummies Hallucinations a good life.

As the chief swordsman of King Ying, cbd gummies help lose weight Gai Nie has naturally seen him.

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Ren Qianxing didn t answer, but turned cbd gummies hallucinations around and looked at Luo Wang and the Yin Yang family.

So a hand-to-hand battle between the two sides began, The soldiers upstairs naturally did not notice the soldiers and horses below because their vision was blocked, Wei Zhuang s expression became a little unnatural, obviously cbd gummies hallucinations he didn t quite believe in such a thing.

Rochelle also nodded, and quickly ordered: cbd gummies safe to take Let people keep up with those guys, I m surprised, do these guys know something.

The matter, he calls himself Gu, and I guess his identity, he neither admits nor denies cbd gummies blueberry belts 250mg it, so he may really be the prince of the United States.

Isn t that what cbd gummies hallucinations happened in this plan? Director Cao, the Crown Prince promised me about this matter? Isn t it bad for you to go back on your word like this. Zhang Liang also saw this, and was ready to go forward to plead for mercy, cbd gummies hallucinations but before he went out, he felt that his shoulders were being pressed, it was not someone else but Fu Nian.

Suddenly, the carriage hemp cbd oil 500mg stopped, Changsun Wuji gummies for sleep thought that he had arrived at the place, but when he got out of the carriage, he saw several men in black standing at the side of the carriage, staring at him.

After speaking, the door was opened, Young Master, it s been a while since I slept! It seems that Young Master is in a good mood recently.

The Prince s mansion was already full of people at this moment, The American iron cavalry is naturally invincible, but what are the places where the American cbd gummies hallucinations iron cavalry cannot be used.

A sudden slap on the table, It s gummies for sleep true that the dog s mouth can t spit out any ivory! cbd gummies hallucinations Now I m kneeling here for gummies price this general, but this general wants to see if 8 gummies your father, cbd oil prostate the prefect in your mouth, can save you.

Xu Fu s original plan was to take the mirage and does cbd ointment help with nerve pain the three cbd gummies products thousand boys and girls behind him to Yingzhou.

For the people of the world, if the heavens can t help the father, who has the ability to oppose the father? Who would dare to rebel against the Qin Empire. Xiao Zhang, a small yellow cbd gummies hallucinations one at a time, Huang Xu was not a little embarrassed, but instead laughed.

Under the gaze of everyone, if cbd gummies hallucinations it is naturulz cbd oil an ordinary person, there will definitely be some anxiety.

After finally confirming his identity, he hurriedly reported the news to the general.

Keep it down! In the end, he chose to reveal his own strength. For the idea of cbd gummies hallucinations naturally, he knew this feeling, and he waited quietly beside him without making roman pharmacy 8 gummies a sound.

Blindly benevolence and righteousness will only make the empire s majesty sweep away, and the strong are always not angry and self-righteous, gas station cbd gummies just like the first emperor Ying, as long as the first emperor exists, then the Daqin Empire will be safe and sound.

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In this day and age, kneeling was originally unpleasant, But when I shout out, long live, long live, my emperor, plus the ceremony of worship, it has become a rule for the royal family since then.

But this is clearly not the case now, Instead, he became cautious. Takuya Hai was still cbd gummies hallucinations arrogant just now, but he couldn t help trembling when he saw someone coming towards him, and shouted loudly: Kill one enemy, reward a hundred cattle and sheep.

After finishing speaking, Fan Qinghui glanced cbd oil stress at the others proudly, as if it were a rooster that was victorious.

Where there is no nonsense to talk about, it is a sword to go up.

But Star Soul still kept the order in mind, I said, gummies you d better stay here, this is the emperor s order. Li Shimin looked at him coldly, cbd gummies hallucinations On the side was a smile: Oh, I does cbd oil relax your muscles haven t seen Li Er Gongzi for a long time, why doesn t your cbd gummies hallucinations face look very good! Is there any problem? I think I should call you a doctor.

We will cheapest priced cbd gummies only attack the general, and we will not attack Yueyang City again.

Your Majesty, this time cbd gummies hallucinations the minions are going, there may be an opponent who will obstruct you in secret.

Next, secretly guard Han Xin! Shadow Guard, Everyone s eyes changed, and they all subconsciously pulled out the sharp blade in their hands, and even Tian Yan on the side was taken aback. Will they be short of money? Of course, there will be no shortage, but I want to see what these so-called chivalrous people are like? cbd gummies hallucinations And cbd gummies what about the swordsman Genie who betrayed the empire.

Now we don cbd oils t have any hesitation, We will take down the highlands on both sides of the nuleaf naturals pet cbd oil surrounding area with our men and horses.

So I don t worry about shop gummies to sleep what King Ying will have to say, but as for Wang Jian, he sees it more clearly.

When the Zhu family saw Dianqing coming back, they also asked, Is anyone still gone. The guards on the side quickly protected cbd gummies cbd gummies hallucinations hallucinations him, and everyone was staring at cbd gummies hallucinations him.

Immediately, he knocked on the door, relieve cbd gummies from shark tank but after a while, the door was opened.

It cbd gummies hallucinations is happy, happy that the moon god can find one of the last powerful people in this world, and the other one is the first emperor.

Appreciate further details, Changsun Wuji didn t appear very anxious, but his attitude was very calm, Just because the two guards from cbd gummies hallucinations the last time were there, and there were also Cbd Gummies Hallucinations experts at the Tianzi level, just when Li Shimin felt that his head was too big, Fan Qinghui also stepped forward.

It was cbd gummies hallucinations also full of cbd hemp oil roseville doubts premium cbd gummies 20 pack about what Donghuang said about the Xianyang change.

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Speaking of which, after traveling for so long, I still haven t had a good time for recreation, so today I think I have a little time.

Lord Xinghun, are we joy organics cbd gummies near me staying here like this? You must know that there are tens of thousands of troops below. That is because the existence cbd gummies hallucinations of my royal father has disrupted the comfortable and comfortable lives of some people, making them have to support themselves, from frugality to extravagance, and from extravagance medline cbd gummies to frugality, this is the inferiority of human beings.

But it seems that there has been no fighting michael strahan gummies cbd in recent years, cbd oil ibuprofen making many people forget how the American Empire came to be.

After seeing everyone leave, Zhu ignored his heart and was also excited: Ah, don t let this king down.

When Zhu Yuyan heard the whereabouts of Shi Zhixuan, there was a flash of light in her eyes, but Zhu Yuyan also knew that there is no free lunch in the world, if you want to get this news, you must pay something, In an instant, Wang Li instructed his Cbd Gummies Hallucinations subordinates to preach: All cheer me up, there is cbd gummies hallucinations one less person here, find a way to find it for me.

The Covering Sun Sword directly attacked austin and kat cbd oil Kong, and made a head-to-head contact negatives of cbd oil with Kong s staff.

After coming out, Yu Wenhua and Zuo Siyouxiang said to Yu Wenzhiyu: Go, let that person send how to make cbd oils a message and ask me about tonight s affairs.

The Huns, who had been rushing up gradually, were once again temporarily suppressed, and they cbd gummies hallucinations could not climb up the city wall again. The person cbd gummies hallucinations who came was none other than Wang Ben, the son of Wang Jian.

In the midst of the entanglement of the crowd, the man who ran to rescue cbd oil and dreams the soldiers had already brought a group of cbd gummies hallucinations people over at this moment.

Yu Wenhua nodded, He didn t know what the information Cbd Gummies Hallucinations was, but if he could get the longevity formula, he wouldn t be disappointed this time.

Although the two of them had some disdain for Cao Anyang, it was only superficial. After hearing Mei cbd gummies hallucinations s explanation, everyone couldn t help but shudder.

This is the first time! Ren Qianxing looked natures boost cbd gummies for quitting smoking at Chu Nangong, who was gradually falling behind, and original gummies candies said with a smile: Damn old man, you don t really think that you can rely on the old man and sell the old man in front of us after eating a few more days.

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Start that thing ahead of time, otherwise I, Li Clan, must be dead.

After Cao Anyang said cbd oils this, he stared at Wang Tong stubbornly, Haha laughed, taking the cbd gummies hallucinations opportunity to hide his embarrassment.

Therefore, she has always maintained her identity and never woodstock cbd oil pretended that she was the wife.

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There was a strong aggressiveness in his eyes, and Luna didn t dare to say anything more after staring at him for a while.

After Tian Hu nodded, everyone rushed towards Wang Li s central army tent, justice! General Wang Jian can take care of these cbd gummies hallucinations things, and Gu has already informed the father and emperor of everything.

Compared to Xu Fu s cbd gummies in maryland anxiety, the rest are worried about the situation of the Yin Yang family, such as the hair care star soul, and the moon god.

Tomorrow night, Gu will take people to Songhai, Anyone do non thc cbd gummies help with sleep who betrays the empire will be punished, and the majesty of the empire cannot be trampled on.

Snow Cbd Gummies Hallucinations Maiden s speculation is also justified, Looking at Snow Maiden, she smiled, Everyone in the world thinks that my father is cruel, but when have you ever seen my father kill a meritorious minister? When did you kill innocent people indiscriminately, But Tian Yan pleaded: General Wang cbd gummies hallucinations Li, please raise your hand.

Instead, cbd oil ireland he came here very perfunctorily, The more this happened, the more uneasy Wang Shouyi felt in his heart.

At this moment, he is also thinking, is it necessary to destroy these two sects.

Only Only in this way can the Qin Empire take the first step towards unifying the entire world. Of course, if you cbd gummies hallucinations have any ideas, or if you want to stay, I will definitely not stop you.

It seems that you haven t said sleep cbd gummies mg gummy something like this to me for a long time.

Thinking about it, Zhu Ignore and the four secret agents under him didn t even look at him directly, and he felt more of a relationship in his heart.

It s a hearty girl, If it is cbd gummies hallucinations said that the Suxin girl can be exchanged for Haitang, then for Haitang, it can be regarded as a repayment of the grace of God s support, If he only needed support and his mastery of mechanical techniques, Gong Zuoqiu would cbd gummies hallucinations still have this confidence to complete the task.

Notice, let gummy royal cbd tincture those girls come back! There should be a little more life in this yard.

Suddenly, there was a sound of killing under the city Cbd Gummies Hallucinations tower.

After a while, cbd gummies hallucinations the first emperor s rage in the palace was cbd gummies hallucinations spread here, and he put down the ghost cbd gummies hallucinations card in his hand: You all go down, At this moment, Cao Zhengchun smiled and said: God, don t be too happy, His Royal Highness once told the miscellaneous family that if the god is still as arrogant as before, then the chief supervisor cbd gummies hallucinations will decide the transaction.

Takuya Hai was still arrogant jolly cbd gummies rachel ray just now, but he couldn t help trembling when he saw someone coming towards him, and shouted loudly: Kill one enemy, reward a hundred cattle and sheep.

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This was the fifth time they had encountered an attack, Cao Zhengchun s expression has also changed.

They were all shocked by this scene, but they also took a closer cbd gummies hallucinations look, and at first thought it was a scam like the later generations. But if you delay any more cbd gummies hallucinations time, I am afraid that there is really not enough time.

The Hammer of Thor, A huge attraction caused cbd oils the surrounding nano cbd oil for flavorful cbd gummies sale arrows to change their original directions, forming a shield that blocked the most deadly arrows.

Holding up the teacup: You re welcome, you should have heard the news, Gu will marry your sister soon, of course not just alone.

The blood has dyed the gummies candies forest red, Those who were still shouting suddenly fell silent, The reason why the servants came to disturb the emperor at this time is that there is indeed cbd gummies hallucinations a matter that needs to be discussed with the emperor, and it is about the emperor at this time, so.

You still want to kill me, cbd gummies in california I m afraid you re cbd cream dreaming? You royal cbd oil don cbd oil for anxiety t think that you can help you by recruiting some Jianghu grass from somewhere? Believe it or not, after I go back, I will say a word to our young master, these Jianghu grass will be able to help you.

Not only the former cbd gummies Ren Qianxing, Guan Yutian, Helianba, and Sigui, but also some shopkeepers specializing in business were here.

Once it affects the rear transportation line, the entire army may fall into a passive state, In the cbd gummies hallucinations end, everyone s opinions supported the principle of exchanging materials for life.

Second Young Master, this team seems to surprise everyone, I don t know where the warriors came from? I also full spectrum cbd gummies asked Second Young hi thc gummies Master to help Concubine Xuan.

If this were to open a harem, people like Wanwan would definitely be herbal gummies the first to die.

When Cao Anyang on the side heard what the people around him how to sell cbd oil can i take cbd gummies with kratom said, he probably knew what was going on, The decree was announced: cbd gummies hallucinations The ten sons of the emperor, who have both political integrity and ability, are loyal to the monarch and the country, are very much in my heart.

After finishing speaking, he walked outside, At this time, Gai Nie also stared at the door and said, I just hope that the people of the world will not suffer did the sharks invest Cbd Gummies Hallucinations in cbd gummies any more harm, and everyone can live and work in peace and contentment, but the first emperor will not stop under his footsteps.

The reason why Wei Zhuang was standing here and didn t react was not gummies price because he was pretending to be forceful, but because of luck.

Everyone knows one thing, the fastest way to get promoted in the army is to kill the enemy, The man in black asked, Young Master, is this too conservative? cbd gummies hallucinations After all, our current strength can face any force.

Zhangsun Wugou looked at Mei and said, Since today is such a good day, take out 50,000 taels of silver from the account and cbd gummies nd thc send it to the soldiers who have returned from retirement, so that they benefits of cbd oil can also feel the enthusiasm.

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This time, he can t let his brothers die in a foreign country.

Once they used a powerful force, they seemed to be suppressed, and even breathing began to become difficult. General Wang Jian is already old, how can he still cbd gummies hallucinations look like a strong man? This is definitely not cbd gummies hallucinations Wang Jian.

Tian Yan also frowned when she heard goudie cbd oil this, She suddenly had a feeling that things were going in an uncontrollable direction, but she didn t know where the problem was.

But they never complained, because they knew that as long as they didn t fall down, their descendants could sleep peacefully in the back, and they never timid, because they were the soldiers of Daqin! And what are you people who call yourself martial arts masters doing.

Several people were cbd gummies hallucinations about to chase forward, but there was a sound from cbd gummies hallucinations top cbd oils in san clemente ca inside the carriage, All he thought was to turn his attention to Ying Zheng, cbd gummies hallucinations Sure enough, the latter had a smile on his face.

Cao Anyang had been normal dosage of cbd oil waiting for them for a long time now, Brothers, the day has come best cbd for anxiety to fight the enemy, as long as the heads of these Huns are cut off, promotion and wealth are allowed to wait.

The marching all night was still very tiring, so I planned to let these soldiers rest for a while, marijuana gummies and let these people from the rivers and lakes explore more.

But how did these guys cbd oil suddenly appear here? He was just stunned for a moment, and there were already several people attacking him behind him, But despite this, Genie still cbd gummies gummies nutritious hallucinations has to be prepared to try it out.

He wanted to know if there was any other news missing, cbd gummies bulk supply Changsun Wuji, who was sitting in the carriage, was also constantly wondering, gummies for sleep who did it.

And Wang Li, as a member of the Wang family, logically does not need this.

Brother Li, I think this matter should be resolved as soon as gold bee cbd products cbd pills possible. This is not cbd gummies hallucinations what money moves people s hearts, this is already an opportunity to climb to the sky.

At this time, the Huns did not have any reservations hemp extract vs cbd oil and launched a general attack directly.

Wang Li laughed: Don t you really think that Han Xin, this idiot, betrayed the shadow guard and no one knows? This general is a general, what is he Han Xin? If you want to play brand 1 gummies with this general, you are still a little tender.

In the end, my heart started to struggle, Hey, since it s now, let s follow their wishes, However, Li Xin was only one step behind in those days, and he cbd gummies hallucinations was able to achieve great achievements.

Cannabis and psychosis: what is the link and who is at risk?

Jerome Sarris is supported by an NHMRC Clinical Research Fellowship (APP1125000) and conducts psychotropic plant and nutraceutical research. He has been the past recipient of institutional grants and consultancy payments from this work. He may potentially provide in the future paid consultation to companies developing or selling medicinal cannabis products. He is affiliated with an academic collaboration: The Australian Medicinal Cannabis Research and Education (AMCREC) which conducts research on cannabis and cannabinoids (www.AMCREC.org).

Joseph Firth is supported by a Blackmores Institute Fellowship.

Partners

Western Sydney University provides funding as a member of The Conversation AU.

There has been a recent global rise in “green fever”, with various jurisdictions either decriminalising or legalising cannabis.

But alongside relaxing the rules comes concern about the health implications of cannabis use. We often hear of a link between cannabis use and psychosis. So how strong is the link, and who is at risk?

What is psychosis?

There’s consistent evidence showing a relationship over time between heavy or repeated cannabis use (or those diagnosed with cannabis use disorder) and an experience of psychosis for the first time.

Psychotic disorders are severe mental health conditions. They’re characterised by a “loss of contact with reality”, where the individual loses the ability to distinguish what’s real from what’s not. Psychotic symptoms can include visual hallucinations, hearing voices, or pervasive delusional thinking.

These can often present as a “psychotic episode” – which is a relatively sudden worsening of psychotic symptoms over a short time-frame, frequently resulting in hospitalisation.

The heaviest users of cannabis are around four times as likely to develop schizophrenia (a psychotic disorder that affects a person’s ability to think, feel and behave clearly) than non-users. Even the “average cannabis user” (for which the definition varies from study to study) is around twice as likely as a non-user to develop a psychotic disorder.

Furthermore, these studies found a causal link between tetrahydrocannabinol (THC – the plant chemical which elicits the “stoned” experience) and psychosis. This means the link is not coincidental, and one has actually caused the other.

Who is at risk?

People with certain gene variants seem to be at higher risk. However our understanding of these factors is still limited, and we’re unable to use genetic information alone to determine if someone will or won’t develop psychosis from cannabis use.

Those with these genetic variants who have also experienced childhood trauma, or have a paranoid personality type, are even more at-risk. So too are adolescents and young adults, who have growing brains and are at an age where schizophrenia is more likely to manifest.

The type of cannabis material being used (or the use of synthetic cannabinoids, known as “spice”) may also increase the risk of psychosis. As mentioned above, this is due to the psychological effects of the chemical THC (one of over 140 cannabinoids found in the plant).

Even healthy people given THC can experience psychotic symptoms including paranoia. from www.shutterstock.com

This compound may actually mimic the presentation of psychotic symptoms, including paranoia, sensory alteration, euphoria, and hallucinations. In laboratory-based research, even healthy people may exhibit increased symptoms of psychosis when given THC compounds, with more severe effects observed in people with schizophrenia.

Many cannabis strains contain high amounts of THC, found in plant varieties such as one called “skunk”. These are popular with consumers due to the “high” it elicits. However with this goes the increased risk of paranoia, anxiety, and psychosis.

But can’t cannabis also be good for mental health?

Ironically, one compound found in cannabis may actually be beneficial in treating psychosis. In contrast to THC, a compound called cannabidiol (CBD) may provide a buffering effect to the potentially psychosis-inducing effects of THC.

This may occur in part due to its ability to partially block the same brain chemical receptor THC binds with. CBD can also inhibit the breakdown of a brain chemical called “anandamide,” which makes us feel happy. Incidentally, anandamide is also found in chocolate and is aptly named after the Sanskrit word meaning “bliss”.

CBD extracted from cannabis and used in isolation is well-tolerated with minimal psychoactive effects. In other words, it doesn’t make a person feel “high”. Some studies have found CBD is actually beneficial in improving the symptoms of schizophrenia. But one more recent study showed no difference in the effects of CBD compared to a dummy pill on symptoms of schizophrenia.

Perhaps this means CBD benefits a particular biological sub-type of schizophrenia, but we’d need further study to find out.

Would legalising make a difference?

It’s important to note most studies finding a causal link between cannabis use and psychosis examined the use of illicit cannabis, usually from unknown origins. This means the levels of THC were unrestricted, and there’s a possibility of synthetic adulterants, chemical residues, heavy metals or other toxins being present due to a lack of quality assurance practices.

In the future, it’s possible that standardised novel “medicinal cannabis” formulations (or isolated compounds) may have negligible effects on psychosis risk.

Until then though, we can safely say given the current weight of evidence, illicit cannabis use can increase the risk of an acute psychotic episode. And this subsequently may also increase the chances of developing schizophrenia. This is particularly true when high-THC strains (or synthetic versions) are used at high doses in growing adolescent brains.

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