Fancy a $5 LSD trip to Wonderland? Perhaps not. You might come back with more than memories of fantastical hallucinations and grinning like a Cheshire cat! A new case report published by two clinicians working in the field of addictions and dual disorders in Israel, Dr. Arturo Lerner and Dr. Shaul Lev-Ran, presents the first ever published record of Alice in Wonderland Syndrome (AIWS) appearing as part of hallucinogen persisting perception disorder (HPPD) after an LSD trip.

As we are in the scientific middle-ages in understanding both AIWS and HPPD, reports like this can promote awareness and understanding of these conditions, and lead to more accurate and effective diagnosis and treatment. Such investigations may also reveal knowledge regarding how we humans perceive reality itself. It’s time to go down the rabbit hole.

Hallucinogen Persisting Perception Disorder

As described in the DSM-V, HPPD is a condition in which a person, after the cessation of intake of hallucinogens, re-experiences certain visuals which were experienced while intoxicated with the hallucinogen. However, Lerner and Colleagues were also the first to report cases of LSD-related flashbacks in which new imagery is experienced. As Dr. Lerner informed us in his Brain Blogger interview:

“Flashbacks (benign return of perceptual disturbances) and HPPD (pervasive return of perceptual disturbances) are misdiagnosed, underdiagnosed or undiagnosed disorders. Misdiagnosing flashbacks and HPPD with organic or functional psychosis sometimes leads to the unnecessary prescription of antipsychotic agents.”

Although the DSM-V does not acknowledge a difference between HPPD and drug-induced flashbacks, with the terms commonly being used interchangeably, both those experiencing these phenomena and those studying it do. As such, Dr. Lerner and colleagues have outlined the two main types of HPPD syndromes:

“…the first Flashback Type we refer to as HPPD I, a generally short-term, non-distressing, benign and reversible state accompanied by a pleasant affect. In contrast, the second HPPD Type we refer to as HPPD II, a generally long-term, distressing, pervasive, either slowly reversible or irreversible, non-benign state accompanied by an unpleasant affect.”

In other words, HPPD I, is of the Flashback Type that either occurs randomly or is triggered by a cue in the environment, and is often considered a relatively trivial “free trip” that generally does not severely or continually interfere with day to day perceptions of reality or cause persistent distress. Hence, HPPD I experiences do not commonly prompt the contact of health professionals.

The case subject had HPPD II, which is quite radically different. Individuals with HPPS II re-experience chronic and persistent altered perceptions of reality, that in rare cases can last a lifetime, and endure:

“… significant distress or impairment in individual, familial, social, occupational or other important areas of functioning. Users are certainly aware of these severe, intruding and disabling consequences of substance consumption and generally actively seek psychiatric help…[and] regularly stop the ingestion of these substances including cannabis derivatives, synthetic cannabis and alcohol.”

While there may be a familial and genetic basis for HPPD it hasn’t been directly explored, yet. Meanwhile, deciphering what is going on in the brain is confounded by the great variability in the types of recurrent hallucinations and different subtypes associated with various psychoactive drugs, indicating that multiple HPPD mechanisms may be at play. For example, brief and benign HPPD I has been reported in chronic, high-potency cannabis users that quit, while severe and highly distressing anxiety related HPPD II has been reported in users of the increasingly worrying legal synthetic cannabis drug, “Spice”.

And although the prevalence of HPPD II (or flashbacks) is currently unknown, initial estimates among individuals who use hallucinogens is approximately 4.2%. And if you are thinking you need to regularly use, or indeed abuse, hallucinogens to get the disorder, you would be wrong, first time users can also develop HPPD.

Alice in Wonderland Syndrome

Inspired by the adventures of Alice in Lewis Carol’s book, AIWS, also known as Todd’s syndrome or Lilliputian hallucinations, is where individuals experience dysmetropsic illusions, i.e., visual distortions that involve the alteration of the size or placement of visual objects.

As described by Dr. Lerner, the man in the case study saw four main visual distortions characteristic of AIWS:

“Cups, books, tables, chairs, and pictures for example, were perceived closer and further away (known as pelopsia and teleopsia respectively). Sometimes they were seen in movement. Body parts (head, arms, and fingers), shoes, a teapot, pens, or a cellular phone for example, were seen smaller or larger than they actually were (known as micropsia and macropsia respectively).”

Oddly, for those with AIWS, the distortions are more common at night, time seems to pass by either at a snail’s pace or passes too swiftly, and those afflicted may also experience a warped perception of sound and touch.

The gentleman in the LSD-induced AIWS case study is not alone. AIWS, being neurological in nature, is also experienced by people with migraines, brain tumors, frontal lobe epilepsy, influenza A infection, Lyme disease, infectious mononucleosis, and in both healthy children and children with migraines, with more girls being affected than boys.

However, no one knows how common AIWS is, largely because most doctors and health professionals, never mind the general public, are even aware of AIWS’s existence. Therefore many people may experience it briefly and benignly and not seek out medical help.

LSD-associated Alice in Wonderland Syndrome

AIWS is generally well-known to be experienced with those under the influence of psychotropics but has never, until now, been reported to remain after drug use has been stopped.

So with regards to the case subject with with HPPD presented as AIWS, what could have went on inside his head to make him feel “mad as a hatter” and seek help?

Dr. Lerner and Dr. Lev-Ran presented an attractive theory in their case report:

“LSD intake might produce short-term limited and reversible damage of the lateral geniculate nucleus (LGN) leading to dysfunction of the parvocellular cells which may modulate the perception of forms and shapes, namely, macropsia and micropsia, and magnocellulars cells which may modulate the perception of movement of still objects, namely, pelopsia and teleopsia.”

The LGN is a part of a brain structure called the thalamus and acts as a relay center for information in the central nervous system’s visual pathway. It is normally described as having six distinctive layers: The first two layers are formed by magnocellular cells and the final four layers are formed by parvocellular cells.

In the case subject, central nervous system dysfunction while taking LSD may have generated an intense electrical current leading to the destruction and/or dysfunction of some of these cells.

As Dr. Lerner adds in his interview:

“It is plausible that destruction of some cells of the LGN may lead to more permanent damage (HPPD II) whereas dysfunction of some cells may lead to temporary side effects (HPPD I).”

As the case subject in question’s symptoms had completely disappeared after a year, without further investigations into AIWS and potentially, studying other drug-induced AIWS cases, we may never know what went on.

Hopefully, articles like the one you are reading now will encourage others having experienced similar symptoms to come forward, and lead to treatments that will ensure rapid and permanent recovery.

As we learn more, as Alice puts it, things will likely get “curiouser and curiouser!”

References

Halpern JH, & Pope HG Jr (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and alcohol dependence, 69 (2), 109-19 PMID: 12609692

G Lerner A, & Lev-Ran S (2015). LSD-associated “Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report. The Israel journal of psychiatry and related sciences, 52 (1), 67-8 PMID: 25841113

G Lerner A, Goodman C, Bor O, & Lev-Ran S (2014). Synthetic Cannabis Substances (SPS) Use and Hallucinogen Persisting Perception Disorder (HPPD): Two Case Reports. The Israel journal of psychiatry and related sciences, 51 (4), 277-80 PMID: 25841224

G Lerner A, Goodman C, Bor O, & Lev-Ran S (2014). Synthetic Cannabis Substances (SPS) Use and Hallucinogen Persisting Perception Disorder (HPPD): Two Case Reports. The Israel journal of psychiatry and related sciences, 51 (4), 277-80 PMID: 25841224

G Lerner A, Rudinski D, Bor O, & Goodman C (2014). Flashbacks and HPPD: A Clinical-oriented Concise Review. The Israel journal of psychiatry and related sciences, 51 (4), 296-301 PMID: 25841228

G Lerner A, Goodman C, Rudinski D, & Lev-Ran S (2014). LSD Flashbacks – The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports. The Israel journal of psychiatry and related sciences, 51 (4), 307-9 PMID: 25841230

Lerner AG, Goodman C, Rudinski D, & Bleich A (2011). Benign and time-limited visual disturbances (flashbacks) in recent abstinent high-potency heavy cannabis smokers: a case series study. The Israel journal of psychiatry and related sciences, 48 (1), 25-9 PMID: 21572239

Liu AM, Liu JG, Liu GW, & Liu GT (2014). “Alice in wonderland” syndrome: presenting and follow-up characteristics. Pediatric neurology, 51 (3), 317-20 PMID: 25160537

Smith RA, Wright B, & Bennett S (2015). Hallucinations and illusions in migraine in children and the Alice in Wonderland Syndrome. Archives of disease in childhood, 100 (3), 296-298 PMID: 25355729

Image via Zastolskiy Victor / Shutterstock.