CB1 agonists can generate hyper-reflexive responses that manifest as eccentric jumping when the animal is slightly perturbed (Dewey, 1986; Patel and Hillard, 2001). It is possible that early studies examining the effect of acutely administered cannabinoids on HIC scores during withdrawal were confounded by these hyper-reflexive responses. Another measure of withdrawal severity in mice is the startle threshold to an electric foot shock. When compared with controls, mice undergoing ethanol withdrawal startle when a lower voltage is applied the cage floor. Using this measure of withdrawal severity, Sprague and Craigmill (1978) found that acute administration of THC, nabilone, or ethanol similarly ameliorated the decreased startle threshold during withdrawal from chronic vapor treatment.
