Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine and several neuropeptides. Recent studies have shown cannabinoid is also a powerful CNS neuromodulator. 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.