Lecture 13. Just Say “Know”: Effects of
Street Drugs on the Brain
Purves et al., Chapter 6, especially the boxes on p. 139 and p. 147.
Psychoactive drugs are a window into how the brain generates consciousness.
They do not create any new physiological actions, but act by modifying
processes that are always going on. By studying their mechanisms and sites of
action, we gain further insights into normal brain function. Most psychoactive
drugs act preferentially at synapses, and we will discuss their actions there.
Stimulants such as cocaine, amphetamines and ecstasy act pre-synaptically to
block the transporters that remove dopamine or serotonin from the synaptic cleft,
thus prolonging the monoamines’ actions at their synapses. Ecstasy is
neurotoxic at high concentrations, killing the serotonin nerve terminals which only
slowly (or not at all) recover. Other drugs, including psychedelics such as LSD
and opiates, act post-synaptically, mimicking normal transmitter actions to
enhance the activity of serotonergic or endorphinergic pathways. Marijuana
mimics the actions of the endogenously released endocannabinoids, and
primarily binds to pre-synaptic terminals to block transmitter release. Alcohol
acts much less selectively, affecting many transmitter systems to induce
confusion, motor incoordination and eventually coma.
1. To learn about the basic effects of cocaine, methamphetamine, ecstasy, LSD,
marijuana and alcohol on normal perception and consciousness.
2. To learn the basic molecular targets of action of these drugs to start to
understand how they act on the brain.
3. To begin to learn how these molecular actions result in changes in human
A. Stimulants with a pre-synaptic action: Cocaine and the amphetamines
Cocaine is typically extracted as a hydrochloride salt from the leaves of
. When extracted in ether to obtain the free base, it becomes
crack which can be smoked. Amphetamines such as methamphetamine are
drugs related to dopamine and also exist as a hydrochloride salt (“speed”) and a
smokable form (“Ice”). Both drugs have similar actions to elevate mood, induce
euphoria, increase alertness and reduce fatigue; however, a cocaine “high”
usually lasts 30-60 minutes, while a methamphetamine trip lasts 12-24 hours.