Cannabinoids in the context of "Licorice"

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators. Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system. A neuromodulator can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Some neuromodulators end up spending a significant amount of time in the cerebrospinal fluid (CSF), influencing (or "modulating") the activity of several other neurons in the brain.

In the United States, the non-medical use of cannabis is legalized in 24 states (plus Guam, the Northern Mariana Islands, the U.S. Virgin Islands, and the District of Columbia) and decriminalized in 7 states, as of November 2023. Decriminalization refers to a policy of reduced penalties for cannabis offenses, typically involving a civil penalty for possessing small amounts (similar to how a minor traffic violation is treated), instead of criminal prosecution or the threat of arrest. In jurisdictions without penalty the policy is referred to as legalization, although the term decriminalization is sometimes used for this purpose as well.

During a wave of decriminalization in the 1970s, Oregon became the first state to decriminalize cannabis in 1973. Ten more states followed by the end of 1978, influenced by the Shafer Commission's endorsement of decriminalization in 1972. By the end of the decade the tide had turned in the other direction, however, and no state would decriminalize again until 2001.