D-cycloserine proved efficient in facilitation of fear extinction in animal research; findings summarized from numerous experiments suppose DCS having visible effect on the NMDA receptor complex responsible for resistance to fear extinction, ultimately assisting the exposure therapy process (Rothbaum, 2008; Kushner et al., 2007; Ressler et al., 2004). These positive findings enabled researchers of psychiatry suppose a similar effect on fear extinction with the application of DCS in combination with exposure therapy for humans (Daveney et al., 2009; Hofman, 2007). However, the body of knowledge on the effect of DCS as a potential adjunct for fear extinction in humans is still small; the modern research is focused on finding proper dosing of DCS that shows effect on fear extinction, researching of the DCS effect on the human cognitive and behavioral mechanisms in the long run as well as identifying the set of conditions under which DCS combined with exposure therapy may have positive effect on treatment of anxiety disorders for humans.

Traditionally, there was a common disapproval of combined pharmacotherapy and psychotherapy in treatment of human anxiety disorders as unimodal treatment appeared more efficient than the mixture of approaches (Zwanzger et al., 2008; Hofmann, 2007). However, initial small-scale and further middle-scale studies reported the comparative advantage of exposure-based CBT and administration of DCS for treatment of described disorders. Though proper dosage of DCS and bounds of the DCs augmentation effects are not yet known, DCS suggests a much more positive effect on fear extinction than the application of exposure therapy alone (Deveney et al., 2009). DCS was found to enhance fear extinction both in animal and human studies, with major gains found in the follow-up treatment (Norberg et al., 2008).

Preclinical studies imply that DCS is effective for blocking the NMDA receptor complex known for its resistance to fear extinction – these findings open a new path for treating DCS not only as an anti-tuberculosis antibiotic, but as an augmentation therapy for psychological treatment procedures for patients suffering from anxiety disorders. This alternative application of DCS may be of substantial value in the field of psychotherapy. Still, it is impossible to deny the range of negative findings both in animal and human studies that either showed no results or suggested the negative impact of DCS on the fear extinction process. Nonetheless, these findings gave a clue to understanding the necessity of acute dosing prevailing over the chronic dosing model as well as sufficient time for memory consolidation upon DCS usage and the necessity of psychological treatment following DCS administration (Hofmann et al., 2006).

Another field of study needed to be accomplished before the decision is made on the DCS application for humans is the extent of generalized extinction that is observed in some experiments. Exposure therapy combined with DCS application shows generalization of extinction to other conditioned stimuli. Such form of extinction proves to be not susceptible to shock-induced reinstatement of fear, which is a great step in psychiatry. This fact found its experimental proof in the work of Davis et al. (2005) – this group of researchers examined several target samples of patients with anxiety disorders and concluded that the fear-potentiated startle of those taking DCS (namely in doses of 15 and 30 mg, without difference in indicators) was the lowest. Even patients who took smaller doses and whose fear-potentiated startle was higher than the one for the most successful group still showed much more progress in fear conditioning than those who did not take DCS at all (Davis et al., 2005).