Endorphins have been associated with analgesia and pleasurable activities. However, the so-called “happy chemicals” are far more complex than initially thought. Research shows that their impact on human behavior is modulatory, with the main goal not being “happiness” but a “return to the most desirable state” – which can be highly context-dependent.

Review of the modulatory functions of endorphins on human behavior and their possible implications in psychiatric conditions.

Pubmed search consisting of the MeSH terms “Endorphins”, “Opioid Peptides”, “Behavior”, and “Psychiatry”.

Endorphins elicit pleasure via stimulation of the release of dopamine from the ventral tegmental area to the nucleus accumbens. They are known to be involved in analgesia and stress response and social interaction. Endorphins can be released in a multitude of circumstances that may seem contradictory – having both inhibitory and stimulating roles in appetite, sexual response, and memory– but are modulatory effects depending on what constitutes homeostasis in each context. Peripheral levels of endorphins have been found low in depression and post-traumatic stress disorder. In schizophrenia, studies suggest that peripheral levels are high during psychosis, low in chronic disease and that naltrexone seems to improve auditory hallucinations. Endorphins may also have a role as markers of treatment response.

Endorphins have a complex role in behavior and homeostasis. These molecules could have implications in psychiatry- given that they are part of our stress response and are released to promote a more “desirable state”. Their role as a marker of illness or response to treatment needs further investigation.

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The expanded suffocation false alarm theory (SFA) hypothesizes that dysfunction in endogenous opioidergic regulation increases sensitivity to CO2, separation distress and panic attacks. In panic disorder (PD) patients, both spontaneous clinical panics and lactate-induced panics markedly increase tidal volume (TV), whereas normals have a lesser effect, possibly due to their intact endogenous opioid system. We hypothesized that impairing the opioidergic system by naloxone could make normal controls parallel PD patients' response when lactate challenged. Whether actual separations and losses during childhood (childhood parental loss, CPL) affected naloxone-induced respiratory contrasts was explored. Subjective panic-like symptoms were analyzed although pilot work indicated that the subjective aspect of anxious panic was not well modeled by this specific protocol.

Randomized cross-over sequences of intravenous naloxone (2 mg/kg) followed by lactate (10 mg/kg), or saline followed by lactate, were given to 25 volunteers. Respiratory physiology was objectively recorded by the LifeShirt. Subjective symptomatology was also recorded.

Impairment of the endogenous opioid system by naloxone accentuates TV and symptomatic response to lactate. This interaction is substantially lessened by CPL.

Opioidergic dysregulation may underlie respiratory pathophysiology and suffocation sensitivity in PD. Comparing specific anti-panic medications with ineffective anti-panic agents (e.g. propranolol) can test the specificity of the naloxone+lactate model. A screen for putative anti-panic agents and a new pharmacotherapeutic approach are suggested. Heuristically, the experimental unveiling of the endogenous opioid system impairing effects of CPL and separation in normal adults opens a new experimental, investigatory area.