Abstract

Introduction

Emerging research suggests that drugs of abuse can alter evaluation of emotional stimuli in ways that could be desirable to users. Specifically, these drugs may positively bias perception of salient stimuli in the environment – either by making bad things seem less bad, or by making good things seem better. Such influences on emotional evaluation may be an important unstudied factor underlying the positively reinforcing properties of drugs of abuse. We recently found that a moderate dose of Δ⁹-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, selectively decreases amygdalar activation elicited by threatening (i.e. angry/fearful), relative to non-threatening (i.e. happy), faces (Phan et al., 2008). Dampened amygdalar reactivity to threatening faces often corresponds to impaired recognition of threat-related facial emotions, and could be indicative of an altered perception of emotional stimuli more generally (Adolphs et al., 1994; Ohman, 2005). However, THC’ effects on evaluation of emotional stimuli have not been thoroughly investigated.

THC’ psychoactive properties derive primarily from its actions at cannabinoid type-1 receptors (CB1Rs) (Cooper and Haney, 2009; D’Souza et al., 2004). CB1Rs are distributed extensively throughout the brain, including the amygdala (Katona et al., 2001; Mackie, 2005). The amygdala plays an important role in mood regulation and perception and processing of emotional information (Price and Drevets, 2010; Vuilleumier and Pourtois, 2007), and it is potently activated by emotionally-salient, particularly threatening, stimuli. Anxiolytic drugs dampen this reactivity, most notably in response to fearful faces (Del-Ben et al., 2011; Paulus et al., 2005), and there is evidence that CB1Rs may mediate some of the therapeutic effects of non-cannabinoid anxiolytic drugs, such as benzodiazepines (Garcia-Gutierrez and Manzanares, 2010). Although few studies have been carried out specifically examining the involvement of CB1Rs in emotional processing in humans, in a recent comprehensive review of the animal literature concerning the function of the endocannabinoid system in cognition and emotion, Zanettini et al. (2011) concluded that ‘endocannabinoid signaling may change the impact of environmental influences on emotional and cognitive behavior rather than selectively affecting any specific behavior’ (for additional reviews of the animal literature see Bambico et al., 2009; Moreira and Wotjak, 2010). Taken together, these data illustrate a potential mechanism by which THC can influence the evaluation of emotional stimuli. Indirect evidence suggests that THC is likely to affect facial emotion recognition. For instance, we previously found that a moderate dose of THC (7.5 mg) reduces amygdalar reactivity to angry and fearful faces (Phan et al., 2008), and a similar trend has been observed by another group using only fearful faces and a slightly higher dose (10 mg) of THC (Bhattacharyya et al., 2010; Fusar-Poli et al., 2009). This profile resembles those of several other drugs of abuse, including alcohol (Gilman et al., 2008), benzodiazepines (Paulus et al., 2005), and +/-3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) (Bedi et al., 2009). More importantly, each of these other drugs has also been shown to impair recognition of threat-related facial emotions (Bedi et al., 2010; Blair and Curran, 1999; Borrill et al., 1987; Craig et al., 2009; Zangara et al., 2002; but see Coupland et al., 2003, who found that diazepam produced non-specific emotion recognition impairments). Based on this evidence, we predicted that THC would impair recognition of threat-related facial emotions.

In addition to altering perception of certain facial emotions, there is also evidence that drugs of abuse can alter the perceived emotionality of other types of salient stimuli in the user’ environment. Indeed, Knowles and Duka (2004) found that social drinkers rate pictures of positive and neutral scenes more positively when they are under the influence of alcohol, and Gospic et al. (2008) found that the opioid drug remifentanil increases the perceived positivity of pictures of neutral scenes; neither drug was found to affect ratings of pictures of negative scenes, however. Furthermore, we recently found that d-amphetamine increases positivity and arousal ratings of scenes independently of their valence and emotional salience (Wardle and de Wit, 2012). Although some studies have failed to detect effects of drugs of abuse (i.e. alcohol and diazepam) on self-reported evaluation of emotional scenes (Patrick et al., 1996; Stritzke et al., 1995), changes in physiological responses to these stimuli were observed, perhaps indicating more subtle influences on emotional processing. For example, reduced skin-conductance responses and startle-reactivity to emotional scenes have been reported following treatment with alcohol (Donohue et al., 2007; Stritzke et al., 1995), diazepam (Patrick et al., 1996), and nicotine (Cinciripini et al., 2006). Thus, there is some indication that drugs of abuse can modulate processing of a variety of salient stimuli, suggesting that THC’ effects on emotional evaluation may extend beyond facial emotion recognition.

It is possible that drugs’ effects on evaluation of emotional stimuli are related to their mood-altering properties. Support for this idea comes from research showing that non-pharmacologically-induced positive mood states enhance recognition of facial happiness (Trevisani et al., 2008), and individuals with lower anxiety are less accurate in recognizing facial fear than higher anxiety individuals (Surcinelli et al., 2006). Previous drug studies have largely overlooked the question of whether drugs’ effects on emotional evaluation are related to their acute effects on mood. It is therefore of interest to investigate this potential link, as these relationships may be useful for understanding how drugs of abuse influence behavior.

In the present study, we examined the effects of acute, oral THC on two measures of emotional evaluation: 1) recognition of facial emotions, and 2) emotional responses to pictures of scenes with varying emotional content. Based on our previous findings and those with other drugs of abuse, we hypothesized that THC would impair recognition of facial anger and fear, and perhaps also increase recognition of facial happiness. Secondarily, we hypothesized that THC would increase the perceived positivity of positive and neutral scenes. Finally, we predicted that these effects would be greatest among those participants who most enjoyed the drug.

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