This review study (1999) finds few, to none, long-term neuropsychological deficits/toxicity that can be attributed to psychedelic (mainly LSD) use.

Abstract

“We collected and reviewed studies in which neuropsychological tests were administered to users of LSD or other hallucinogens. Interpretation of the studies is limited by various confounding variables, such as subjects’ premorbid cognitive and personality function and prior use of other substances. At present, the literature tentatively suggests that there are few, if any, long-term neuropsychological deficits attributable to hallucinogen use. To better resolve this issue, however, it will be important to study larger samples of chronic, frequent hallucinogen users who have not often used other types of drugs.”

Authors: John H. Halpern & Harrison G. Pope

Summary

1. Introduction

Hallucinogenic drugs of plant origin have been used for thousands of years by various peoples around the world, and in the last 50 years have been supplemented by a wide range of synthetic compounds. In the 1990s, hallucinogen use among youth increased significantly.

It is becoming increasingly apparent that chronic abusers of psychedelic drugs experience severe personality changes. These changes may range from a schizophreniform psychosis to an organic brain syndrome.

The residual effects of hallucinogens are controversial. Some investigators suggest that hallucinogens are unlikely to cause lasting impairment, while others suggest that they may cause chronic psychosis in predisposed individuals.

The controversy regarding the residual effects of hallucinogens continues to the present day. DSM-IV lists several hallucinogen-related disorders, but does not comment on whether individuals with hallucinogen-related disorders would be expected to demonstrate residual cognitive impairment, much less an organic brain syndrome.

2. Methods

We searched the Medline database for papers on hallucinogens, and found 67 candidate papers. Of these, 19 papers actually administered neuropsychological tests to hallucinogen users, and 23 papers had references to additional papers. We excluded studies examining acute hallucinogen use, studies examining polydrug use, individual case reports, and studies that commented on the residual effects of hallucinogens but did not include formal neuropsychological testing. This reduced the number of studies under consideration from 42 to 9.

3. Results

Blacker et al. (1968) found that 21 LSD users had increased alpha, beta, delta, and theta activity and increased visual evoked response amplitudes at the dimmer intensities in comparison to unmatched controls, but acknowledged that their results were inconclusive due to lack of premorbid testing.

McGlothlin et al. (1969) found that 30 LSD users had worse spatial orientation than 30 controls, but that they did not differ from the control group on IQ, concept formation, speech perception, time perception, tactual performance, tactual recognition, motor ability, or spatial orientation.

Subjects were excluded if they had used other hallucinogens, opiates, marijuana, or had engaged in ‘moderate’ use of oral sedatives and stimulants. The authors chose 16 non-LSD-exposed controls matched for age, sex, and education, and administered neuropsychological tests. The results showed no significant differences between groups, and the only positive finding was that spatial orientation scores in the LSD group correlated negatively with their ranking on the number of LSD ingestions.

Subjects who had been taking LSD for 12.2 months had lower organic brain functioning than controls, although neither group was in psychiatric treatment.

In an uncontrolled study, 32 of 40 chronic LSD users scored within the ‘brain-damaged tests’ on the Wechsler Adult Intelligence Scale (WAIS), Halstead Battery, and the Trail Making Test. In a controlled study, 15 LSD users performed inferior to 15 controls on several measures of the Reitan battery.

The performance of third group subjects on the Trail Making Tests A and B was significantly lower than the performance of the first two groups on these tests.

Nine self-identified MDMA users were administered a series of neuropsychological tests. Most tests showed no impairment as compared to population norms, but several subjects displayed mild to moderate impairment on the Wechsler Memory Scale. Grob et al. (1996) assessed 15 members of a legally sanctioned Brazilian religion, the Uniao do Vegetal (UDV), who regularly use a plant-based hallucinogen, hoasca, as a sacrament. The members scored significantly lower than controls in the novelty-seeking and harm-avoidance domains of the Tridimensional Personality Questionnaire.

4. Discussion

Several studies have tentatively reported impairment on certain neuropsychological measures in hallucinogen users as compared to controls, but most studies failed to control for premorbid attributes and failed to control for use of other illicit drugs and alcohol.

Some studies had methodologic problems, such as a toxic screen to exclude subjects with evidence of illicit drug use at or near the time of testing, but they generally found few residual effects. It seems unlikely that hallucinogens produce major residual neuropsychiatric impairments.

The nine neuropsychological studies assessed only 9 – 40 hallucinogen users each, and some of the subjects had used hallucinogens only a single occasion. It is possible that subtle toxic effects were missed, and the tests employed in the available studies may have failed to ‘tap’ specific areas of cognitive deficits.

While hallucinogens may cause a neurotoxic impingement upon central serotonergic systems, atypical antipsychotic medications have proven neuroprotective to such damage in preclinical models, and LSD and DOM have counterintuitively proven similarly protective due to the very same 5-HT2a agonism.

5. Conclusion

Future studies should take care to address the various methodological problems reviewed above, and should include a large sample of subjects with extensive hallucinogen exposure. Also, timed information processing tasks might yield further evidence of functionally significant deterioration.

There are indigenous populations outside of Western industrialized culture that use hallucinogens extensively but rarely use other drugs. These populations may be suitable candidates for standard neuropsychological tests, which can be augmented with non-verbal assessments to further control for cultural and language differences.