Archive for the ‘ Journal Papers ’ Category

Alterations in the Nocturnal Sleep Cycle Resulting From LSD

The mechanics of the unique psychedelic mindstate remain tantalizingly unclear, but there are several interesting clues. For instance, LSD enhances REM sleep associated with dreaming. During a typical night, we experience about four or five periods of REM sleep, increasing in duration toward the end of the night. During REM sleep, the activity of the brain’s neurons is very similar to the activity during waking hours, but the body is paralyzed and cannot move. It was dubbed “paradoxical sleep” when it was first discovered, as this brain activity seemed to indicate that the subject was not sleeping at all.

A subject was observed during a normal sleep cycle of approximately seven hours, which was interrupted briefly one hour after she fell asleep in order to administer a placebo or 30ug of LSD. First, the inactive placebo was given. Her progression through the four stages of sleep may be seen in the top graph, with periods of REM sleep indicated by the dark black bars. We can see that most of her REM sleep occurs during lighter Stage 1 sleep.

While the initial REM episodes a half hour or so after waking are similar, after 30ug of LSD the second REM episode occurs much earlier and lasts almost three and a half times longer than the corresponding REM episode after placebo. Many more micro-REM episodes lasting only ten to twelve seconds burst into sleep for several hours after the LSD has taken effect.

In general, LSD can prolong the first or second REM episode and cause these REM micro-bursts, but only if given in low doses immediately before sleep or one hour after sleep begins. Doses that are too high simply cause the sleeper to awaken as they are about to transition to REM sleep.

Joseph N. Muzio, Howard P. Roffwarg, Edward Kaufman, Alterations in the nocturnal sleep cycle resulting from LSD, Electroencephalography and Clinical Neurophysiology, Volume 21, Issue 4, October 1966, Pages 313-324.

The Neurobiology of Psychedelic Drugs

An excellent review paper has appeared in Nature Reviews: Neuroscience entitled “The neurobiology of psychedelic drugs: implications for the treatment of mood disorders”. Here’s the abstract:

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

As a result, Nature has decided to highlight some related reading in their Blog Focus: Hallucinogenic drugs in Modern Medicine and Mental Health with four great articles.

The secret history of psychedelic psychiatry Highlighting the early advances of Dr. Humphrey Osmond and other pioneers of psychedelic psychotherapy.
Serotonin, Psychedelics and Depression
Investigates the relationship between the action of psychedelics and current theories of depression, both which rely on the neurotransmitter serotonin.
Ketamine for Depression: Yea or Neigh?
Investigating the potential of the NMDA antagonist ketamine as a breakthrough treatment for depression.
Visions of a psychedelic future
A Western scientist’s experience with the psychedelic brew ayahuasca.

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial

A great paper just came out in the Canadian Medical Association Journal, dealing with the ability of cannabis to combat neuropathic pain. Neuropathic pain is thought to be caused by damage to the nervous system, and often does not respond to conventional painkillers. It is estimated that 1-2% of the adult population is affected, and patients with this chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.

Suffice to say that most of the time this isn’t suggested by doctors and dispensed by prescription. So does it actually work? 21 adults with post-traumatic or postsurgical neuropathic pain completed the study, and were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% THC). They assigned the various strengths of cannabis as part of a “crossover trial”, where each subject would receive one of the concentrations randomly for a two week period. After four two-week periods and random “crossovers” to other potencies, everyone had tried every potency.

Participants inhaled a single 25-mg dose of cannabis through a pipe three times daily for the first five days in each two-week period, followed by a nine-day washout period before the next trial. Daily average pain intensity was measured using an 11-point scale, and effects on mood, sleep, quality of life, and adverse events were recorded.

And the results? Turns out that you need decent pot for pain relief, but it doesn’t have to be an insanely potent strain. Lower potency cannabis did not significantly reduce pain, but the 9.4% THC cannabis reduced pain, improved ability to fall asleep, and improved quality of sleep. The beautiful outcome is that cannabis containing 10% THC is widely available and only 75mg a day (slightly over two grams a month) is needed to cause statistically significant improvements for those suffering chronic pain.

Mark A. Ware, Tongtong Wang, Stan Shapiro, Ann Robinson, Thierry Ducruet, Thao Huynh, Ann Gamsa, Gary J. Bennett, Jean-Paul Collet, Smoked cannabis for chronic neuropathic pain: a randomized controlled trial, Canadian Medical Association Journal, Volume 182, Number 14, 2010, Pages 694-701.