This study will examine the effects of a single low dose of the 5HT2A agonist LSD (Lysergic Acid Diethylamide) (13 µg) or placebo in individuals who are or are not explicitly told what drug they will receive. Although it is known that expectancies strongly influence subjective responses to most drugs, no studies have examined expectancies on response to a very low dose of LSD. This is especially important in the context of 'microdosing' of drugs. People who practice microdosing typically do so with strong expectations of positive effects, making it difficult to determine whether there is a pharmacological effect. To minimize expectancies in the laboratory, participants are usually not told exactly what drug they will receive (i.e., double-blind), but given a range of possibilities. In the present study, the study team will test half the subjects under single-blind conditions, where the participants (but not the research assistant) will know exactly what they are receiving. Other subjects will receive the usual instructions. Healthy volunteers will receive either a marginally detectable dose of LSD (13 micrograms) or placebo, under conditions where they i) know for sure what drug they are receiving or ii) where the identity of the drug is uncertain. Four groups of subjects (N=12 each) will attend single 4-hour laboratory session. The study team will examine subjective and behavioral responses to the drug in each of four conditions (Known-Drug; Known-Placebo; Uncertain-Drug; Uncertain-Placebo).

Expectancies are known to influence responses to psychoactive drugs. The study team and others have shown previously, using a balanced placebo design, that expectancies influence responses to alcohol, nicotine, caffeine, stimulant drugs, and cannabinoids. In these studies subjects are randomly assigned to one of four conditions: Expect the drug and get the drug; Expect the drug and get placebo; Expect placebo and get the drug; Expect placebo and get placebo. This allows researchers to separate pharmacological effects from expectancy effects.

Recently there has been much discussion about the role of expectancies specifically in responses to psychedelic drugs. Expectancies are especially important in the use of very low doses, referred to as 'microdoses'. These doses are typically at or below the threshold of detectability, but users take them with strong prior beliefs that the drugs improve mood and cognition. The beneficial effects have been difficult to demonstrate under laboratory conditions, perhaps because in the laboratory the drugs are administered without the explicit expectation of benefits, and the administration of the drugs is to some extent blinded. The present study is designed to separate the pharmacological effects of a low dose of LSD from effects that are influenced by expectancies.

Inclusion Criteria:

• English Fluency
• High school education or higher
• BMI between 19-30 kg/m2

Exclusion Criteria:

• Individuals with a medical condition contraindicating study participation as determined by the study physician (e.g., liver disease, abnormal EKG, liver or cardiovascular disease)
• High blood pressure (>140/90)
• Current suicidal ideation or suicide attempt in past 12 months
• Past year severe substance use disorder
• Personal or first-degree relative with history of psychosis
• Currently taking any psychiatric medication (for conventional antidepressants must be off for ≥ 2 weeks)
• Active panic disorder
• Severe obsessive-compulsive disorder
• Severe post-traumatic stress disorder
• Women who are pregnant or planning to become pregnant