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Isr J Psychiatry Relat Sci - Vol 48 - No.1 (2011) Arturo G. Lerner et al. Benign and Time-Limited Visual Disturbances (Flashbacks) in Recent Abstinent High-Potency Heavy Smokers: A Case Series Study

Arturo G. Lerner, MD,1,2 ,Craig Goodman, PhD, 1 Dmitri Rudinski, MD, 1 and Avi Bleich, MD1, 2

1 Lev Hasharon Mental Medical Center, Pardessya, Israel 2 Sackler School of , Tel Aviv University, Ramat Aviv, Israel

may induce a state of intoxication popularly referred ABSTRACT to as a “trip” (4). These “trips” or substance-induced are generally transient and reversible states Eight high-potency heavy cannabis smokers who that are typically accompanied by perceptual distur- fulfilled DSM-IV-TR criteria for cannabis dependence bances. The mind-altering effects are experienced in sought treatment for outpatient detoxification. a clear sensory-conscious state, while awake and alert During routine psychiatric interview they reported the and generally in the absence of confusion (5-8). A well presence of visual disturbances when intoxicated and known, unique and intriguing side effect associated no prior history of LSD use. They all communicated with the use of synthetic such as lysergic the persistence of visual disturbances after ceasing acid diethylamide-LSD and LSD-like substances is the cannabis use. Seven categories of visual disturbances partial or total recurrence of the perceptual disturbances were described when staring at stationary and moving which previously appeared during intoxication, in the objects: visual distortions, distorted perception of absence of recent use (9-11). These experiences are distance, of movement of stationary and accompanied by full insight and can be short or long- moving objects, color intensification of objects, term (10, 11). The original intoxicating may dimmed color, dimensional distortion and blending be “good” (pleasant) or “bad” (unpleasant). In the same of patterns and objects. Patients reported having 2-5 way, the perceptual recurrences recapitulate the prior different categories of flashbacks up to 3-6 months “trip” or intoxication that was experienced as either after cessation of cannabis use. The described “good” or “bad.” A previous “good” trip, however, does phenomena may be interpreted as a time-limited not always predict or ensure a “good” recurrence (10, benign side effect of high-potency cannabis use in 11). Common recurrent visual disturbances attributed some individuals. A combination of vulnerability and to this complex syndrome are geometric hallucina- use of large amounts of high–potency cannabis seem tions, false perception of movement in the peripheral to contribute to the appearance of this condition. visual fields, flashes of colors, intensified colors, trails Conclusions from uncontrolled case series should be of images of moving objects, positive afterimages, halos taken with appropriate caution. around objects, and micropsia (12). At least two subtypes of this syndrome have been reported. The first is . It is a short term, tran- sient, recurrent, spontaneous, reversible and generally visual benign experience. Experienced LSD users gener- Introduction ally look at these recurrences as a “free trip,” an aspect Hallucinogens encompass a group of naturally-occur- of the psychedelic dimension, and do not seek psychiat- ring substances from vegetable (1) and animal (2) ric assistance after experiencing these types of episodes. origins as well as synthetic chemical agents (3) which Certain individuals may experience the recurrence of

Address for Correspondence: Arturo G. Lerner, MD, Lev Hasharon Mental Health Medical Center, POB 90000, Netanya 42100, Israel [email protected] ; [email protected]

25 Benign and Time-Limited Visual Disturbances (Flashbacks) in Recent Abstinent High-Potency the same single flashback while other perhaps more attempted to stop cannabis use in the past without suggestible subjects may have a variety of them. The professional assistance. Patients included in the report second is persisting perception disorder met the DSM-IV-TR criteria for cannabis dependence (HPPD). This is long-term, spontaneous, intermittent (12). They reported the need for markedly increased or continuous, pervasive and either slowly reversible amounts of cannabis to achieve desired effect, cannabis or irreversible. This disorder is entirely different from was smoked over longer periods than was intended, the benign flashback (10, 11). HPPD is a condition in there were unsuccessful efforts to stop or control its which the re-experiencing of one or more perceptual use, a great deal of time was spent to obtain cannabis symptoms causes significant distress or impairment in and finally social, occupational and recreational activi- social, occupational or other important areas of func- ties were impaired (12).They communicated cannabis tioning (12). HPPD often occurs in individuals with no intoxication with perceptual disturbances (12), the prior psychopathology, and may be extremely debili- intake of high concentrated cannabis (22) since start- tating. Hallucinogen users are usually aware of these ing cannabis use, a period of at least five years severe, intruding and disabling consequences of LSD and a daily consumption (“joints” and water pipes) of consumption and generally actively seek psychiatric at least three times a day (i.e., morning, noon or after- help. HPPD seems to be part of a large spectrum of noon and evening). They had no prior use of LSD or non-psychopathological and psychopathological expe- other hallucinogenic substances. All patients had pre- riences reported by hallucinogen users (10, 11). vious compulsory military service, no prior police or Whether or not the use of cannabis alone can be asso- criminal records, and were not married. Four of the ciated with persisting perceptual abnormalities has been patients reported smoking cannabis alone. The other debated. Investigators tend to agree that cannabis can four reported occasional use of , MDMA, and precipitate perceptual recurrences in subjects who had also fulfilled full criteria for dependence (12). previously used LSD and that it is unlikely that canna- Visual disturbances during intoxication were reported bis alone can provoke recurrent perceptual disturbances only after being interviewed for treatment and were not (13-15). However, there are reports of accurately recalled. Treatment was not sought due to (16, 17), perceptual symptoms experienced during can- visual disturbances. They associated the precipitation nabis intoxication (18, 19) and short-term spontaneous of visual disturbances only and strictly by cannabis recurrent visual disturbances (20) after the suspension smoking. Other consumed legal (nicotine and alco- of cannabis use alone. Reliability of recurrent canna- hol) and illegal (ecstasy and cocaine) substances were bis associated visual experiences has been critically not associated with the perceptual disturbances. None questioned. It should be noted that according to DSM- of the patients had any co-morbid medical disease or IV-TR the diagnostic criteria of cannabis intoxication co-occurring psychiatric disorders. Neurological and allows for a diagnosis of “with perceptual disturbances” ophthalmologic examinations were intact. Two patients (12). If perceptual disturbances can be observed dur- had a family history of . ing intoxication by cannabis alone (12, 21), it is plau- sible that some predisposed and susceptible cannabis Demographic data heavy smokers using high concentrated cannabis (22) Mean age of patients was 29.25 years old (S.D.=2.25), may partially or totally recapitulate the previous per- mean education was 13.13 years (S.D.=1.55), mean ceptual experience in the absence of present cannabis duration of non-use was 82.25 days (S.D.=40.6), mean use. We present the cases of eight high-potency heavy duration of cannabis use was seven years (S.D.=1.69), users of cannabis without a prior history of LSD use and mean number of previous attempts of cessation or who reported the presence of benign persisting visual detoxifications was 0.625 (S.D.=0.74). All patients were disturbances after stopping . white males of Jewish Israeli descent, were currently employed, and had a middle class socioeconomic status.

Method Detoxification and follow-up Clinical data (THC) was present in urine Eight patients were examined after seeking treatment samples prior to initiation of detoxification. No other for cessation of chronic cannabis use. Four of them psychoactive substances were identified. All patients

26 Arturo G. Lerner et al. underwent uncomplicated outpatient cannabis detoxi- when staring at stationary and moving objects: visual fication using only minimal symptomatic medication distortion (slightly blurred object), distorted perception like small doses of (23) and careful use of of distance (objects were slightly seen closer or distant), . They continued working when under- of movement of stationary and moving objects going treatment reflecting low severity or control of the (slow movement), color intensification of objects (slightly detoxification process. After detoxification and follow- more intensified), dimmed color (slightly less intensified), up, substances of abuse were not identified in random dimensional distortion (objects were slightly seen smaller urine samples. Two out of eight patients relapsed after – micropsia, or larger – macropsia) and blending of pat- two months. One of the relapsing subjects reported terns and objects. All eight of the patients experienced having visual disturbances again when intoxicated. The visual distortions of objects, six had distorted perception remaining six abstinent patients reported flashbacks up of distance from the object, five of the eight reported to six months after stopping cannabis use. Interestingly, having illusions of movement of stationary and moving two patients who had a family history of schizophrenia objects, two reported color intensification of objects, two reported longer duration of recurrences. None of the reported dimmed color, two slight dimensional distor- subjects were interested in pharmacological treatment tion of objects and two patients reported blending of for the flashbacks or psychotherapy. None of the six patterns and objects. Number of flashbacks from each abstinent patients revealed the presence of flashbacks category and overall number were difficult to calculate. at the one-year follow-up visit. The most frequently reported type of flashback and the last to disappear was visual distortions of objects. Flashbacks The term flashback is used instead of HPPD, due to the benign nature of the visual recurrences (9-11). Discussion Individuals reported the presence of flashbacks similar to While the precise mechanisms underlying cannabis- those visual disturbances which appeared during intoxi- associated perceptual disturbances are unknown, there cation. There was not a clear period of latency between is some knowledge indicating similarities with some the appearance of visual disturbances during intoxica- proposed mechanisms related to LSD associated percep- tion and the continuation of flashbacks during detoxifica- tual disturbances. Serotonin neurotransmission appears tion and follow-up. The average time of persisting visual to be involved in the genesis of both acute and persist- disturbances experienced by the participants following ing LSD-induced perceptual disturbances. The acute detoxification was 11.75 weeks (S.D.=5.80). Flashbacks effects of LSD seem to be mediated through a 5-HT2 were perceived as benign, generally short term (from a postsynaptic partial activity (24). Similarly, fraction of a second up to several minutes), spontaneous the acute appear to be related to (without identified triggers), recurrent, non-distressing serotonergic systems. Although the main acute phar- and entirely reversible. The accompanying affect was macological effects of cannabis are mediated through pleasant. Prodromal symptoms (aura) did not precede the receptors, it is known to severely disrupt flashbacks (11). Flashbacks started with a frequency of a serotonergic neurotransmission. This disruption could few times a day (mean=11.75, S.D.=5.80) and their inten- be responsible for most of the cannabis effects on cog- sity was not experienced as disturbing or painful. After nition and perception (25, 26) and could be associated initial presentation, flashbacks usually decreased in fre- with the ability of to produce perceptual dis- quency and intensity, with a tendency to slowly wear off. turbances such as depersonalization (16, 27). Moreover, The accompanying affect usually disappeared along with marijuana smoking, but not placebo smoking, was able the recurrence. Full insight, reality testing and judgement to produce depersonalization in healthy subjects (28). were always maintained. Users looked upon the flashback Therefore this mechanism could also attempt to explain as a kind of “free trip” or curious experience. Patients acute cannabis associated visual disturbances. reported having from two up to five different categories The chronic and persisting effects of LSD, hallucino- of flashbacks which appeared when staring at stationary gen persisting perception disorder and flashbacks (10, and moving objects. Distortions were described as mini- 11), may closely resemble the previous hallucinogenic mal, "almost imperceptible" and very slight in nature. experience, implying that a mechanism related to the Seven categories of visual disturbances were described original one may be involved. The basic mechanism

27 Benign and Time-Limited Visual Disturbances (Flashbacks) in Recent Abstinent High-Potency underlying this syndrome appears to be a vulnerability may also support the estimation that persistent visual or a predisposition of LSD users to continue the cen- disturbances may be related to disinhibition of visual tral process of visual imagery after the image has been processors via impairment of GABA transmission by removed from the visual field (29). An LSD-generated inhibitory interneurons. It is still unclear how serotonin intense current (30) may provoke the destruction or systems are involved in the phenomena. dysfunction of cortical serotonergic inhibitory inter- Cannabis-related compounds and the anandamider- with GABA-ergic outputs and lead to the per- gic system seem to be involved in areas of visual infor- sistence of the visual imagery due to chronic disinhibi- mation processing (38). Impairment of visual sensory tion of visual processors (8). Thus, it is plausible that data has also been suggested (38).The physiological and high-potency cannabis (22) that affects serotonergic pathophysiological roles of the central nervous endog- neurotransmission (25, 26) could provoke a similar enous cannabinoid system are not completely under- effect in some vulnerable and predisposed subjects. stood (39). The suspected influence and participation There is more data indicating the possible seroton- of psychoactive on acute and persistent ergic involvement in the genesis and perpetuation of visual perception and central information processing visual disturbances. The appearance of visual phe- need to be elucidated. nomena resembling flashbacks (palinopsia) in patients High-potency cannabis may have some influence without a previous or hallucinogen in the development of the presented visual side effects. exposure after risperidone, and The THC content varies between different sources and administration (31-33) has been reported. These tran- preparations of cannabis (22). Sophisticated cultivation sient visual disturbances have been attributed to the such as hydroponic farming and plant-breeding tech-

5HT2A blocking properties of these agents. Heightened niques have greatly increased the potency of cannabis sensitivity to side effects and reduced 5HT2A serotonin products (22). In the and an average stimulation rather than increased 5HT2c stim- contained about 10 mg of THC. Now a joint made out ulation have been proposed as explanations for these of potent subspecies may contain around 150 mg of intriguing phenomena (31). THC or 300 mg if laced with oil (22). Given Medications shown to be beneficial in the treatment the fact that the effects of THC are dose related (25) of persisting visual disturbances may provide additional and most of the on cannabis was carried out in support for serotonergic involvement. Alleviation of per- the 1970s using doses of 5-26 mg of THC (40), modern sisting visual disturbances after administration of ser- predisposed and vulnerable cannabis smokers may be traline was attributed to the down regulation of 5-HT2 exposed to doses of THC greater than in the past and receptors (29). Reboxetine also appears to be helpful in risks and consequences might be greater (41). the treatment of some subjects complaining of persist- Cannabis-induced flashbacks appear to be a benign ing visual recurrences with depressive features (34). side effect. It remains unclear if it is an uncommon and

Reboxetine may have an α2 adrenoreceptor modulating infrequent associated feature or if it has been under- effect on both noradrenaline and serotonin release (35). reported by patients due to its benign nature or under- Reboxetine may also affect the reuptake of serotonin diagnosed by clinicians. A combination of vulnerabil- and lead to down regulation of 5-HT2 receptors resem- ity and use of large amounts of high-potency cannabis bling the improvement of persisting visual disturbances seem to contribute to the appearance of this condition. after administration of SSRIs (29, 34). Benzodiazepines’ Additionally, those predisposed individuals seem to effectiveness in the treatment of persisting visual distur- present a returning pattern of visual disturbances bances may be related to activity at cor- whenever cannabis is smoked. The return of visual dis- tical serotonergic inhibitory interneurons with GABA- turbances in relapsing subjects and the continuation of ergic outputs (5, 6). Clonazepam which may improve visual disturbances in those who suspended cannabis persisting visual occurrences (10), HPPD with anxious intake for short periods in the past and during treat- features (11) and depersonalization (36) may also affect ment may support the existence of this suggested pat- serotonergic system and enhance serotonergic trans- tern. It should be reiterated that patients only applied mission (37). This effect may secondarily lead to down for cannabis detoxification treatment. Information regulation of 5-HT2 receptors, which may contribute to regarding the presence of visual disturbances was iden- the HPPD symptoms remission (29). This amelioration tified and collected during routine clinical interview.

28 Arturo G. Lerner et al.

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