Loren L. Miller

Cannabis: Neural Mechanisms and Behavior – a Theoretical Review

The hypothesis is advanced that marihuana and espedaily Δ9-tetrahydrocannabinol, impair certain aspects of hippocampal neural functioning which are necessary for normal cognitive operations

Effects of δ9-THC, LSD-25 and scopolamine on continuous, spontaneous alternation in the Y-maze

The effects of δ9-THC, LSD-25 and scopolamine on continuous, spontaneous alternation of the hooded rat in the Y-maze were determined. LSD and scopolamine decreased the number of arm entries (responsivity) while concomitantly reducing percent alternation. THC however, reduced responsivity and percent alternation more at the lower dose (1 mg/kg) when compared to control than at the higher dose (3 mg/kg). Only scopolamine induced a significant increase in stimulus perseveration. The results are discussed in relation to the advantages afforded by the continuous spontaneous alternation procedure.

Marijuana and memory impairment: effect on free recall and recognition memory.

The effect of marijuana on memory was evaluated by presenting two groups of 17 male volunteers with lists of repeated or nonrepeated words following administration of a single marijuana cigarette containing 14 mg delta9-THC. An immediate free recall, final free recall and recognition memory test followed. Results indicated that marijuana significantly decreased immediate and final free recall but only slightly influenced recognition memory. Rate of acquisition on the repeated lists was the same for both groups. Long term retention of encoded information was not influenced by marijuana. The shape of the serial position curves departed slightly from those reported by other investigators in that some effects of the drug on the recency portion of the curve were noted. Both internal and external intrusions were elevated under marijuana.

Effect of 9 -THC on the open-field activity of the rat.

Using the open-field activity of the hooded rat as a model of overall activity, the dose-response and time-action effects of doses of Δ9-THC which did not adversely affect spontaneous activity or behavior on appetitively motivated tasks were studied. Subjects received two exposures to an open field one week apart. Prior to the first exposure subjects were treated with small doses of Tween 80-water. At 30 min or 3 h prior to the second exposure subjects were treated with Tween or Δ9-THC in doses which ranged from 0.5–5 mg/kg. Results indicated that Δ9-THC affected various indices of open-field activity such as grooming, sniffing and ambulation differently depending on the time after injection. Rearing and defecation were affected similarly by THC independent of post-injection intervals.

Effects of propranolol on marihuana‐induced cognitive dysfunctioning

Paid male volunteers were allowed to smoke marihuana cigarettes calibrated to deliver a dose of 25 µg per kilogram of delta‐9‐tetrahydrocannabinol (Δ‐9‐THC). All subjects were given propranolol or placebo (administered in a double‐blind fashion), in 4 divided doses beginning 24 hours before and ending 2 hours prior to smoking. Marihuana smoking resulted in significant disruption in the recall of narrative material and moderate impairment in performance on a modified version of the Reitan Trail Making test. Stroop‐Color Word performance was not affected by marihuana. Propranolol, a beta adrenergic blocking agent, failed to interact with marihuana to reduce its disruptive effects on any of the tests.

Marijuana: dose effects on pulse rate, subjective estimates of intoxication, free recall and recognition memory.

The effect of marijuana on memory as measured by free recall and recognition, pulse rate and self ratings of intoxication was evaluated in 16 male volunteers. Marijuana containing 0, 5, 10 or 15 mg delta9-THC was administered to all subjects by smoking in 4 sessions separated by a 1 week interval. Free recall was reduced in a dose related manner by the drug, but recognition memory was unaffected. A 2 sec word presentation rate produced inferior recall in comparison to a 4 sec rate, but this variable did not interact with drug condition. Intrusion errors increased following intoxication but this effect was not systematically related to dosage of delta9-THC. Both pulse rate and self ratings of intoxication increased with dosage.

Marijuana: effects on storage and retrieval of prose material.

In a two phase design, an attempt was made to differentiate the effect of marijuana on the storage and retrieval of prose material. In the first phase, 40 male subjects were administered a single 500 mg marijuana cigarette containing 2.1% Δ9-TCH or a placebo cigarette. Fifteen minutes after smoking, they listened to and at the same time read a narrative passage of approximately 200 words in length. Subsequently, an immediate free recall test was given in which subjects were required to write down as much of the story as they could remember. The second phase was conducted 24 h later. Marijuana and placebo subjects were randomly subdivided into four groups with half of the subjects participating in the same drug condition as occurred on day one while the others switched drug state. Fifteen minutes after smoking, all subjects recalled the passage pressented on day one and then were given 24 questions concerning facts and events in the story which could be answered in a few words. These questions served as retrieval cues. Following this, a new passage was presented in the same manner as occurred on day one. After an immediate free recall test, another cued recall test was administered.Results indicated that marijuana reduced immediate recall under both cued and uncued conditions in comparison to placebo. No relative cued recall advantage was found in the marijuana groups for the old or new story and marijuana produced only a moderate decrement in recall of the old story on day two. However, marijuana given in the second phase significantly reduced memory for items recalled in the initial phase irrespective of drug or cueing condition in phase one, suggesting that retrieval was also affected. Some decrement in recall of the new story did occur as a function of drug state change in group M-P. This effect was related to the serial position of input items. Serial position did not interact with drug state under any other recall condition.

Marijuana and memory impairment: the effect of retrieval cues on free recall☆

In an attempt to ascertain the effect of retrieval cues on recall deficits which occur following intoxication with marijuana, 40 male volunteers were presented with word lists following the smoking of a single one gram marijuana (0.94% delta 9 -THC) or placebo cigarette and then were required to recall these words immediately after presentation. Recall occurred under a condition in which cues representative of to-be-remembered words were present or in an uncued condition. Results indicated that recall was depressed following marijuana administration under both cued and uncued conditions with cues being only mildly effective in reversing the recall deficit. There was no increase in the number of internal intrusions under marijuana, but the number of external intrusions was significantly elevated under the cued conditions.

Marijuana: dose-response effects on pulse rate, subjective estimates of potency, pleasantness, and recognition memory.

34 experienced marijuana users were divided into four equated groups of eight subjects each based on recognition memory test performance. One week later each group was retested following administration of marijuana containing 0, 5, 10 or 15 mg delta9-tetrahydrocannabinol. A dose-related effect of marijuana on pulse rate and subjective measures of potency and pleasantness occurred. Ratings of potency and changes in pulse rate were highly correlated, but this relationship did not hold within a given dosage group as determined by partial correlations. No effect of marijuana on the distribution of hit and false alarm rates or confidence ratings during the recognition memory test was noted.

Marijuana: Effects on free recall and subjective organization of pictures and words

The free recall of pictures and words was compared following the administration of marijuana or placebo in a multitrial free recall task. Since pictures are thought to be registered in both visual and verbal memory stores with this encoding being mediated by some form of mental imagery, it was predicted that marijuana would produce a greater deficit in word recall in comparison to picture recall because the drug has been reported to facilitate imagery. A trend in the opposite direction followed intoxication; picture recall was inferior to word recall in the later stages of acquisition. Although overall recall was inferior under marijuana, no differences were found between the treatment conditions in subjective organization as determined by a variety of clustering measures. Recall performance following marijuana intoxication was positively related to level of recall performance in the placebo condition.