Another hallucinogen proves to be beneficial. Discovered in 1943 by Albert Hofmann, Lysergic acid diethylamide (LSD) was developed by accident. I mean, Albert was studying lysergic acid compounds; and produced LSD with the sole purpose of it becoming a respiratory stimulant to induce breathing, which he put aside for five years.¹ When he returned to it, he accidentally absorbed some through his skin (as is the method of LSD administration) and experienced a dreamlike state.¹ Three days later, he purposefully ingested a moderately large dose of LSD and detailed a fantastic trip in his book LSD, my problem child (free pdf online).¹ There, in 1943, he immediately recognized that “[LSD] would have to be of use in pharmacology, in neurology, and especially in psychiatry.”^1(p.14) It’s about time we started listening.

Three takeaways to tell your friends:

• This study involved 19 human subjects taking visual tests, some after receiving LSD.²
• LSD improved learning in response to rewards and punishments.²
• Subjects that received LSD were more likely to explore multiple responses regardless of reward while adapting better to reward learning when the task became complex.²

What does LSD do in our bodies? Briefly, LSD binds to one of the many stimulating serotonin receptors.³ Serotonin, a neurotransmitter involved in emotions, has several receptors. This LSD-serotonin receptor is located widely throughout the brain.³ LSD activates them all at once.

In this study, researchers examined the effects of LSD on human subjects in a learning experiment.² The experiment goes as follows²:

1. Subjects are presented with three shapes simultaneously on a computer screen.
2. They choose one.
3. The screen rewards them with a green smiley face.
4. The three options appear again.
5. They choose a different option.
6. The screen punishes them with a red frowning face.
7. The three options appear again.
8. …this repeats for 40 trials.

This is the acquisition phase. The subjects are learning the experiment. Importantly, they will not always be rewarded with a green smile after selecting option one or punished with a red frown after selecting option two. Once they choose their first, second, and third choices, they will be rewarded and punished based on the order they were picked for the rest of the 40 trials of acquisition:

• Option 1: Rewarded 75% of the time, punished 25% of the time.
• Option 2: Punished 75% of the time, rewarded 25% of the time.
• Option 3: Rewarded 50% of the time, punished 50% of the time.

The goal is that during the 40 trials, they are learning to choose option one more frequently and choose options two and three less. Then, they reversed it.

For the next 40 trials, the most-rewarded option one became the most punished option, and the most-punished option two became the most rewarded option. The neutral 50/50 option three remained the same. This tested the subjects’ abilities to adapt to new information, for they had to abandon the reward system they just learned. Overall, LSD enhanced the subjects’ abilities to recognize the pattern of rewards and punishment, especially during the reversal trials (Table 1).²

Additionally, other factors were considered, like the subjects’ exploration of options and sensitivity to the reward/punishment. The LSD subjects showed strong abilities to explore each answer thoroughly, regardless of the previous answer (stimulus stickiness) (Table 1).² During acquisition, LSD subjects experienced lower (reinforcement) sensitivity to reward outcomes, showing their more exploratory nature (Table 1).² However, during reversal, LSD subjects experienced higher (reinforcement) sensitivity to reward outcomes, highlighting their improved learning abilities (Table 1).² Lastly, LSD subjects who had an increased reward learning rate during acquisition struggled initially adapting to reversal.² However, given the LSD subjects’ ability to outperform the untreated subjects in reward and punishment learning during reversal (Table 1),² it’s clear that the LSD group effectively learned the reversed rewards after briefly failing to unlearn the reward system from the acquisition trials.²

Overall, LSD improves learning when associated with rewards and punishment while increasing exploratory behavior.

	During Acquisition/ While learning the task	During Reversal/ When the reward switches options	Overall
Reward learning	Increased	Increased	Increased
Punishment learning	No effect	Increased	Increased
Stimulus stickiness	Decreased	Decreased	Decreased
Reinforcement sensitivity	Decreased	Increased	No effect

Note: The amount of LSD given to each patient was 75µg directly into their bloodstream. Doses range from mild (25-75µg) to moderate (75-150µg) to high (>150µg).⁴ If you decide to try it, consider having a trusted, sober friend there to guide you. Be safe.

REFERENCES

1.         Hofmann A, Hofmann A. LSD, my problem child; and, Insights/outlooks. Oxford: Beckley Foundation Press : Oxford University Press; 2013. xii, 232 p. p.

2.         Kanen JW, Luo Q, Rostami Kandroodi M, Cardinal RN, Robbins TW, Nutt DJ, et al. Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans. Psychol Med. 2022;53(14):1-12.

3.         Nichols DE. Psychedelics. Pharmacol Rev. 2016;68(2):264-355.

4. The LSD Dosage Guide | Determining the Right Dose of LSD [Internet]. Trippingly. 2020. Available from: https://www.trippingly.net/lsd/the-lsd-dosage-guide