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Case notes z Persisting perception disorder

A persisting perception disorder after use

Zoë Ellison-Wright MBBS, MSc, MRCPsych, Ben Sessa MBBS, BSc, MRCPsych

Hallucinogen persisting perception disorder is a disorder of uncertain aetiology occurring mainly after ‘classical’ hallucinogen use (ie mescaline, psilocybin, dimethyltryptamine and LSD) use. Here, the authors describe the case of a boy with similar symptoms developing after he reported using cannabis seven times.

annabis use Symptoms seemed tired, irritable and anxious. Cmay lead to The patient said he had used Subsequently, he said that he had acute intoxica- cannabis with his friends on one smoked cannabis on several occa- tion, depend- occasion four weeks previously. sions (prior to four weeks ago), and ence or The following day he felt different recalled being told that the psychosis but and said that his perceptions were cannabis may have had other things some reports altered. He gave some examples, mixed in with it, possibly LSD. suggest that it may be associated eg when he looked at things, they with the type of perceptual seemed closer or further away than Initial management disorder usually described after they should or appeared distorted It was considered that he may be hallucinogen use.1 Hallucinogen or ‘wave about as though made of developing psychosis. He was pre- persisting perception disorder jelly’. He occasionally saw strange scribed risperidone 0.5mg per day. (HPPD) is an uncommon or rare colours and lights. When he wrote, He became increasingly agitated. consequence of ‘classical’ hallu- his sentences appeared distorted. The risperidone dose was cinogen misuse. Patients experi- If he focused on things for too increased over the next two weeks ence persistent and distressing long then the colours changed and to 4mg and he was also prescribed perceptual changes, such as visual the objects appeared to turn into lorazepam 1mg up to three times distortions, auras or halos.2 We other things. daily as needed. describe the case of a boy with sim- He also said that when he Despite the increase in risperi- ilar symptoms after minimal heard sounds, they sometimes done, his symptoms continued to cannabis use. echoed or continued for a long worsen. His mother thought his period in his head. He said that had increased while taking Presentation when he touched things, there was it, so four weeks after starting it A 15-year-old white British male was a delay before he actually felt them risperidone was reduced and referred by the Early Intervention and he also described sensations stopped. Psychiatric inpatient in Psychosis Service with possible going through his body such as tin- admission was considered, but the psychotic symptoms. He said he gling, heat or cold. Sometimes he family preferred intensive commu- had been well until four weeks pre- felt that he was taller than normal. nity support. He was referred for a viously. He had no past medical or As well as these perceptual dis- paediatric opinion to exclude an psychiatric history. However, he turbances, he said his thoughts organic cause for his symptoms. said he had always had a tendency were ‘all over the place’. He some- He was admitted as a day patient to worry about things. times had thoughts in his head for investigations. He had a neu- He was studying for his GCSEs that he could not control that rology assessment, a CT and hoped to study graphic design seemed like someone else’s think- which was normal and later an in the future. He had good peer ing and were ‘gibberish’. EEG, also normal. relationships. He lived with his par- He did not describe auditory No organic cause for his psychi- ents and two younger siblings. His or unusual tastes or atric symptoms was discovered, but mother described herself as very smells. His mother noticed that he he described painless haematuria anxious. A paternal uncle suffered was withdrawn, and ‘lost his spark for the last year; he had not told from . and his mischievousness’. He also anyone until the paediatrician

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Persisting perception disorder z Case notes

4 interviewed him because he was response. Sertraline was reduced Diagnostic criteria not concerned about it. A bladder to 25mg per day. tumour was found on ultrasound. One year later his anxiety symp- A Following cessation of use of a hallucinogen, He underwent transurethral resec- toms had resolved and the percep- the re-experiencing of one or more of the per- tion of bladder. Results confirmed tual symptoms, though still present ceptual symptoms that were experienced while a complete resection of transi- to some degree, were not impair- intoxicated with the hallucinogen (eg geometric tional cell carcinoma with a very ing. He had coped well with A-Level hallucinations, false perceptions of movement good prognosis. exams. Sertraline was discontinued. in the peripheral visual fields, flashes of colour, He said he was not using drugs and intensified colours, trails of images of moving Progress remained scared of them. He was objects, positive , halos around objects, and ) Within five days of stopping risperi- discharged from the service. B The symptoms in Criterion A cause clinically sig- done his anxiety symptoms had nificant distress or impairment in social, occupa- greatly reduced, although he con- Discussion tional, or other important areas of functioning tinued to describe constant percep- The symptoms experienced by the C The symptoms are not attributable to another tual abnormalities – in particular, boy, as noted by his mother, shared medical condition (eg anatomical lesions and grainy vision and a dream-like state. similarities to those described in infections of the brain, visual ) and are His functioning began to improve HPPD. This is a disorder of uncer- not better explained by another mental disor- and two weeks later he was able to tain pathophysiology, first recognis- der (eg delirium, major neurocognitive disorder, go out and visit his friends. He able in reports of drug use in the schizophrenia) or hypnopompic hallucinations gradually returned to school, but late 19th century,2 defined in the Table 1. Hallucinogen persisting perception disorder: DSM-5 found concentration difficult. American Diagnostic and Statistical diagnostic criteria He took his GCSE exams, and Manual DSM-4 and updated in despite continuing to experience DSM-5 (see Box 1).5 It typically visual hallucinations, eg flashes of symptoms he coped well and occurs after use of classical hallu- colour or moving images, halos achieved good results. Following cinogens, although there is also around objects, macropsia (objects his exams, lorazepam was gradu- some contemporary emerging evi- appear larger than normal which ally stopped and he started in the dence that other drugs with mild may cause the person to feel Sixth Form. He continued to expe- psychedelic properties, ie MDMA smaller) or micropsia (objects rience perceptual abnormalities, (3,4-methylenedioxy-methamphet- appear smaller than normal which which were worse when he was amine), may also rarely produce a may cause the person to feel tired or stressed, and increased similar HPPD-like syndrome.6 larger). For diagnosis the symp- after starting his A-Level courses. The classical hallucinogens toms need to cause significant dis- He had also become preoccupied include LSD (lysergic acid diethy- tress or impairment. Other about cannabis, feeling very anx- lamide), DMT (N,N-dimethyltrypt- diagnoses need to be excluded, eg ious that he might inhale cannabis amine), DOB (dimethoxybromo- brain lesions, visual epilepsies, that someone else was smoking. amphetamine), psilocybin and delirium, schizophrenia or He even felt anxious if he saw a pic- mescaline. They act by binding to hypnopompic hallucinations (hal- 7 ture of cannabis on a computer the 5-HT2 serotonin receptor. lucinations which occur when wak- screen. He knew that this was an Although cannabis can cause some ing from sleep). The symptoms irrational fear. hallucinogenic effects, it is not may last for last for weeks, months, Six months later, following a considered a classical hallucino- or years. second opinion, he decided to try gen. The main psycho-active ingre- DSM-5 notes that HPPD occurs cognitive behavioural therapy dient is tetrahydrocannabinol primarily after LSD use, but not (CBT) and sertraline 25mg per day (THC) which acts in the brain on exclusively, and some instances was started, increasing to 50mg the cannabinoid receptors, CB1 may be triggered by use of other 8 5 after a week. Three weeks later he and CB2. substances, eg cannabis. complained of tiredness and nose According to DSM-5, the disor- bleeds. It was postulated that ser- der follows cessation of hallucino- Prevalence traline may be contributing to nose gen use and is associated with A series of reports of subjects with bleeds3 because SSRIs may increase re-experiencing some of the per- HPPD-like symptoms were system- the risk of bleeding by blocking the ceptual symptoms which occurred atically reviewed by Halpern and uptake of serotonin into platelets, during intoxication. The main per- Pope in 2003.2 They concluded that impairing the platelet haemostatic ceptual changes described are there was considerable variability in

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Case notes z Persisting perception disorder

the reports. For example, in a fol- Treatment Some strains of cannabis are now low-up study of 247 subjects who HPPD can cause considerable dis- very rich in THC and can produce had received LSD in conjunction tress for some individuals for a pro- marked psychedelic experiences. with psychotherapy or in research longed period. A large number of The boy said that he recalled protocols in the 1960s, only 2% of treatments have been tried but being told that the cannabis he subjects described symptoms sug- have mainly been described in case had taken may have had other gestive of HPPD.9 Overall, studies series rather than controlled trials. things mixed in with it, possibly reported that between 0–77% sub- According to these reports, some LSD. If this was the case, then his jects suffered HPPD after LSD use cases have benefitted from using symptoms might have been due to with the higher rates in studies sunglasses, psychotherapy, behav- HPPD after minimal LSD use. where LSD was used illicitly rather ioural modification or pharmaco- Although a wide variety of contam- than therapeutically, there was logical agents.2 The latter have inants have been described in ongoing illicit drug use, or subjects included antipsychotics (haloperi- cannabis (eg sand, sugar, glass had premorbid psychiatric illness. dol, trifluoperazine, olanzapine), bead, industrial chemicals and antiepileptics (carbamazepine), phencyclidine),11 it has been sug- Differential diagnosis clonidine, benzodiazepines, or gested that hallucinogens are As well as the differential diag- SSRIs (sertraline).2 Conversely, more likely to be added by users noses noted in DSM-5, they sug- some reports have described wors- rather than dealers. There is the gested that others to consider were ening of symptoms with antipsy- possibility that the boy’s friends normal visual experience (eg see- chotics (including risperidone) or adulterated the cannabis; however, ing floaters), , continued SSRIs.2 More recent reports have given the very volatile nature of drug intoxication, affective disor- suggested beneficial treatment LSD crystals, the likelihood of it ders, malingering, hypochondria- with the antiepileptic lamotrigine being effectively administered via sis, anxiety disorders with or tolcapone, a catechol-O-methyl- smoking in a joint is very low depersonalisation/derealisation or transferase (COMT) enzyme indeed. Nevertheless, it is possible post-traumatic stress disorder. inhibitor used in the treatment of that he was spiked with LSD some Parkinson’s disease.10 other way, eg in food or a drink. Pathophysiology In this case, the patient’s symp- The cause of HPPD remains uncer- Clinical case toms worsened while he was pre- tain but three possibilities have The boy described in this case scribed risperidone. This is been suggested.2 Firstly, individuals experienced perceptual symptoms consistent with reports of risperi- might have a heightened awareness similar to those reported in HPPD. done exacerbating HPPD, to normal visual phenomena. His symptoms were persistent, last- although it may also have wors- Secondly, the perceptual symptoms ing months, distressing and impair- ened his symptoms through its side might represent memories of the ing (to the extent that psychiatric effects of agitation and akathisia. acute intoxication experience inpatient admission was considered accompanied by a high level of at one stage). Although he was ini- Second opinion emotional distress. Thirdly, the tially suspected to have a prodro- During the course of the illness, symptoms could be due to some mal psychotic illness (such as the boy was referred for a second neurological change induced by schizophrenia), he did not experi- opinion. At that time he said he the drug exposure, eg disinhibition ence auditory hallucinations or experienced permanent ‘visual of visual processing related to loss first-rank symptoms, he retained snow’ and he frequently saw of serotonin receptors on insight into his visual experiences ‘floaters’ which looked like two- inhibitory inter-neurons. With and he did not benefit significantly dimensional bubbles. At times the regard to this last hypothesis, from taking risperidone. walls appeared distorted or Halpern and Pope comment that if This raises the possibility he ‘breathing’. He described deper- HPPD was due to some ‘kindling’ might have developed an HPPD- sonalisation and derealisation at phenomenon then one might like disorder induced by minimal times. These symptoms were worse expect that it would be more com- cannabis use, perhaps in common when his eyes were closed or when mon in individuals with a large with the very small number of cases feeling stressed, eg when ‘bogged number of LSD exposures rather described in the literature of HPPD down by school work’. than just a few – however, this does in subjects who reported previous He said prior to the onset of the not appear to be the case.2 cannabis but not hallucinogen use. illness he had smoked cannabis

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Persisting perception disorder z Case notes

seven times. The first five times he distortions, HPPD should be con- Dr Ellison-Wright is a Consultant smoked a joint with friends, it was sidered in the differential diagnosis Child and Adolescent Psychiatrist, a relatively low dose and not an and a careful history of substance Dorset HealthCare University unpleasant experience. The next use should be taken. Treatment Foundation Trust, and Dr Sessa is a two times he smoked cannabis at options remain empirical but if the Consultant Child and Adolescent high dose in a water pipe, without symptoms are regarded as anxiety- Psychiatrist, Addiction Substance tobacco, and he and his friends related then CBT approaches or Misuse Services, Weston-Super-Mare experienced a very intense reac- SSRIs may be considered. tion. He felt highly depersonalised, Alternatively, if the symptoms are Declaration of interests detached, dissociated and para- viewed as neurological due to cere- There are no conflicts of interest noid, and was hallucinating. bral receptor changes then other declared. The opinion was that a few pharmacological treatments exposures to cannabis would be include antipsychotics, antiepilep- References very unlikely to result in these tics or benzodiazepines. 1. Gaillard MC, Borruat FX. Persisting visual hallucinations and in previously drug- symptoms. It was thought likely HPPD has been described addicted patients. Klin Monbl Augenheilkd that the experience was a psycho- mainly after use of the classical hal- 2003;220:176–8. logically frightening one and that lucinogens such as LSD. There are 2. Halpern JH, Pope HG. Hallucinogen persist- ing perception disorder: what do we know he had subsequently focused on it a few reports of symptoms starting after 50 years? Drug Alcohol Depend and concentrated on the potential after cannabis use, although a 2003;69:109–19. negative outcomes which had causative role remains speculative. 3. Lake MB, Birmaher B, Wassick S, et al. therefore persisted. Therefore his In this case, the patient may have Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J diagnosis was considered to be an smoked a strain of cannabis very Child Adolesc Psychopharmacol 2000;10:35–8. anxiety disorder, similar to post- rich in THC producing a marked 4. Andrade C, Sandarsh S, Chethan KB, et al. traumatic stress triggered by a trau- psychedelic experience, or he was Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians matic psychological event. It was in some other way spiked with and a reconsideration of mechanisms. J Clin considered that a genetic risk fac- LSD. It is possible that his symp- Psychiatry 2010;71:1565–75. tor was his mother’s anxious tem- toms were exacerbated by anxiety 5. American Psychiatric Association. Diagnostic perament. Treatment with CBT associated with an erroneous and and Statistical Manual of Mental Disorders, 5th edn. Arlington, VA: American Psychiatric and an SSRI was recommended. overly risk-aversive attitude to the Publishing, 2013. In support of this diagnosis, the dangers of classical hallucinogens. 6. Litjens RP, Brunt TM, Alderliefste GJ, et al. boy became more preoccupied However, the relative low risk of Hallucinogen persisting perception disorder and the serotonergic system: a comprehensive that he might be inadvertently clinically significant and function- review including new MDMA-related clinical exposed to cannabis, which he ally impairing HPPD, even with cases. Eur Neuropsychopharmacol 2014;24: recognised as an irrational fear. prolonged classical hallucinogen 1309–23. doi: 10.1016/j.euroneuro.2014.05.008 [Epub 2014 May 20.] His symptoms also improved with use, must be considered in the 7. Pierce PA, Peroutka SJ. Hallucinogenic drug sertraline treatment. contemporary context of the interactions with neurotransmitter receptor During the course of his psychi- potential therapeutic benefits for binding sites in human cortex. atric treatment, he was diagnosed psychedelic-drug therapy.12 Psychopharmacology (Berl) 1989;97:118–22. 8. Pertwee RG. The diverse CB1 and CB2 recep- with an apparently incidental blad- A number of studies worldwide tor pharmacology of three plant cannabinoids: der carcinoma and he underwent are investigating the role for using delta9-tetrahydrocannabinol, cannabidiol and 9 surgery for this with remarkable drugs such as psilocybin, LSD and delta -tetrahydrocannabivarin. Br J Pharmacol 2008;153:199–215. stoicism. However, in a teenager, other psychedelic drugs, as well as 9. McGlothin WH, Arnold DO. LSD revisited: a the effects of persistent haema- cannabis, as agents to facilitate psy- ten-year follow-up of medical LSD use. Arch turia, a cancer diagnosis and the chotherapy for patients with a wide Gen Psychiatry 1971;24:35–49. 10. Leo H, Melanie S, Martin R, et al. surgical treatment must have been range of mental disorders, which Hallucinogen persisting perception disorder considerable, despite the good show that psychedelic drugs can be (HPPD) and flashback – are they identical? J prognosis. This may have resulted safely administered in the medical Alcoholism Drug Depend 2013;1:121. 12 11. McLaren J, Swift W, Dillon P, et al. Cannabis in displaced and projected anxiety setting. Emerging evidence potency and contamination: a review of the exacerbating his symptoms. shows that even when used in the literature. Addiction 2008;103:1100–9. recreational context, the majority 12. Sessa B. Shaping the renaissance of psyche- Conclusion of users of psychedelic drugs do delic research. Lancet 2012;380(9838):200–1. 13. Krebs TS, Johansen P-Ø. Psychedelics and In patients presenting with visual not demonstrate clinically signifi- mental Health: a population study. PLoS ONE hallucinations or perceptual cant mental health problems.13 2013;8(8):e63972.

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