Oksitosiini on nisäkkäillä esiintyvä hormoni, jolla on hyvin merkittävä ja laaja rooli sekä perifeerisessä hermostossa että aivoissa. Intranasaalisesti annetun oksitosiinin on todettu mm. lievittävän pelkoa ja lisäävän luottamusta sekä anteliaisuutta. Oksitosiinin ja mm. äidillisen rakkauden sekä taipumusten sitoutua moni- tai yksiavioisesti on todettu liittyvän yhteen. Hyvin, hyvin merkittävä välittäjäaine siis. (Ks. lisää englanninkielisen wikipedian oksitosiiniartikkelista.)
Viime aikoina myös MDMA:n vaikutuksia käyttäytymiseen on alettu tutkimaan tältä kantilta - ja vaikuttaa siltä, että käyttäjien kokemat prososiaaliset "rakastan kaikkia"-fiilikset ovat ainakin osittain (ellei täysin) oksitosiinivälitteisiä (ja tämä antaa vankempaa tieteellistä pohjaa MDMA-terapian revisioimiselle):
Dumont & al. - Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.
Social Neuroscience, Vol. 4, Issue 4, 359 - 366
MDMA (3,4-methylenedioxymethamphetamine or “ecstasy”) is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.
Johansen & Krebs - How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationaleA plausible mechanism of action for oxytocin-mediated prosocial effects was reported in a study that showed that oxytocin attenuates the amygdala response to novel social encounters (Baumgartner et al., 2008). In addition, a recent report demonstrated that attenuation of the amygdala inhibits excitatory flow from the amygdala to brain stem sites mediating peripheral fear response (Huber, Veinante, & Stoop, 2005). For the case of MDMA, oxytocin may thus reduce anxiety related to social interaction, effectively promoting social behavior (Amaral et al., 2003; Rosen & Donley, 2006). When this is combined with its stimulating effects and mild enhancement of sensory input, it is not surprising that MDMA has become such a popular ‘‘club drug’’ (Dumont & Verkes, 2006; Vollenweider et al., 2002). Although the results of animal research strongly support our conclusions, the findings of the present study should be considered exploratory and some limitations should be addressed.
Firstly, we measured oxytocin concentrations in blood, whereas cerebral spinal fluid oxytocin concentrations are expected to provide a more direct relation to the central effects. Indeed, a delay between maximal subjective effects (tmax 60 min) and measured peak plasma oxytocin concentration (tmax 110 min) was observed. Congruent with this finding, several reports have suggested that the release of oxytocin from the posterior pituitary gland into the peripheral circulation is preceded and driven by central, autostimulatory oxytocin release in the parvoventricular nucleus and supraoptic nucleus (Ludwig & Leng, 2006; Armstrong, 2007; Amico, Tenicela, Johnston, & Robinson, 1983). However, this remains speculative as the relationship between peripheral and central oxytocin release has not yet been defined (Landgraf & Neumann, 2004).
Secondly, we assessed subjective prosocial effects. Future studies should employ objective measures of social interaction such as the Trust Game or Dictator Game (Sanfey, 2007) to verify that subjects not only perceive themselves as being friendlier but in fact show increased social behavior.
Thirdly, to reduce the variance in observed oxytocin concentrations, future studies should also consider dosing MDMA according to body weight, rather then administering a fixed dose. Moreover, oxytocin concentrations should be assessed concurrently with MDMA and subjective assessments and between 20 and 95 min, where the current study did not assess oxytocin concentrations but did find the most pronounced subjective prosocial effects, to assess the onset of peripheral oxytocin level elevation and its relation to prosocial effects.
Lastly, although our results suggest that oxytocin is involved in MDMA’s prosocial effects in humans, these results remain tentative as the current design cannot determine whether oxytocin really mediated MDMA’s prosocial effects. This should be verified in an MDMA interaction study using an oxytocin receptor antagonist such as Atosiban (Uvnas-Moberg, Bruzelius, Alster, & Lundeberg, 1993), although several issues regarding oxytocin receptor antagonism remain (Chini & Manning, 2007).
Journal of Psychopharmacology, Vol. 23, No. 4, 389-391 (2009)
1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance;
2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and
3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations.
Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy.
