Alcohol activates endogenous opioid receptors, potentiating dopamine release which increases the rewarding effects of alcohol. These regulatory sites can each produce positive allosteric modulation, potentiating the activity of GABA. Environmental enrichment increases neurogenesis in aged rodents by potentiating neuronal differentiation and new cell survival. Many sedative/hypnotic drugs act by binding to and potentiating GABA-A receptors. IL-33, which activates and maintains eosinophils, also exerts a similar potentiating effect on Siglec-8-induced apoptosis. The different chemicals might be potentiating synergistic effects (1+1=3). Combination with other depressants has a potentiating effect and can cause overdose. There has been interest both in potentiating and inhibiting the activity of PHD2. It appears to work by potentiating A2 adenosine receptors. Platelet activation in turn degranulates and releases factor V and fibrinogen, potentiating the coagulation cascade. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. Nitrous oxide potentiating the haematological toxicity of methotrexate has also been documented. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success. Incorporation of known potentiating modifications yields the commercially available oral progestin medrogestone (4).