Smokers of cannabis have observed the memory-impairing effects for as long as the drug has been consumed. However, it was not understood how this property was induced until very recently. Even now, the literature is not even nearly complete. Delta-9 THC is the drug that has been proven to produce the majority of this effect.
Here is the full scientific article if you wish to download it.
In this study, the role of CB1 receptors in glutamate and GABA (gamma-Aminobutyric acid) signalling was investigated. The results are curious: THC seems to inhibit the release of GABA, but not through altering GABA receptors. The implications of this are unclear at this time. THC is a full agonist at GABA terminals, another surprising result. This expands the scope of the endocannabinoid system substantially and will be the topic of much scientific endeavour.
The conclusion of the paper is that through GABA inhibition in the hippocampus, delta-9 THC can exert modulatory effects that produce impaired memories.
The hippocampus is a part of the brain that is vital to the processing of short-term memories and the consolidation of short-term memories into long-term memories. It is thought that this series of processes is in part mediated by the endocannabinoid system.
However, to quote the authors regarding THC in the hippocampus: “surprisingly little is known of its physiological actions on specific intact neural pathways in the CNS”. In other words, THC is known to have memory inhibiting effects in the hippocampus, but nobody knows how.
GABA neuron axon terminals are one form of the end to an axon. When a neuron connects with another, it sends signals along its own arm, or axon, until it reaches the synapse or the gap between the axons. It is at this axon terminal that the GABA terminals studied in this paper were found. When a signal passes along one of these axons in the hippocampus, it uses the neurotransmitter GABA to pass the signal to the next neuron over the synaptic gap.
Close to these GABA terminals are CB1 receptors. THC was thought to be a partial agonist of these receptors, or bind to them occasionally. This paper has proven that they are, in fact, full agonists. The evidence leads the authors to suggest that THC inhibits GABA release in the synapse but does not change GABA uptake or the GABA receptors.
The consequence of GABA release inhibition in the hippocampus is thought to be a change in which signals are passed along. In a process as tightly controlled as memory consolidation, it is unsurprising that altering the threshold for a signal to be passed would alter the way that a memory is formed and stored. While the mechanism and model for this modulation is still out of the reach of scientists, it is useful to know how the processes that underlie the overall effect work.
When CB1 receptor agonists like THC are blocked by CB1 receptor antagonists, the memory disruptive effects are not found. This indicates the importance of the receptor and agonists are in memory, and now the process by which the ECS is involved has been partially elucidated.
The memory disrupting effects of delta-9 THC have for the first time a model of action. By inhibiting GABA release in the hippocampus, delta-9 THC can alter how memories are formed and consolidated.