Thursday, April 20, 2017


BOL-148 is the 2-brom derivative of LSD. There is a Bromine (Br) in place of Hydrogen at position 2.

In spite of its close structural relationship to LSD, BOL-148 has no psychedelic effects. Among the LSD analogs, BOL-148 is especially important because it indicates that substitution at the 2-position can change the activity of the whole molecule, as outlined by the studies below.

In 15 healthy males, doses of 75-110 ug/kg BOL-148, which 100X exceed an effective dose of LSD, caused no change in pupillary dilation, patellar reflex, or blood pressure (Isbell et al., 1959). BOL-148 did not alter the behavior of 6 individuals with schizophrenia, when given at 10X the dosage of active LSD, although for BOL-148 these doses may have been too low to observe any effect. BOL-148 1 mg twice a day for 2 weeks, or 5 mg for 3 days had no evident effect on their psychoses (Turner and Merlis, 1958).

There is evidence of the contrasting pharmacological effects of LSD and BOL-148 on the EEG. While LSD affects the EEG in doses of 100 ug/kg, BOL-148 in doses of 100+ ug/kg are reported to be without effect on the EEG, and generally when there is no EEG effect, no drug effect is expected. BOL-148 did not cause any sign of the fast electrical activity or alerting behavior seen with injections of LSD in cats, even when doses of up to 100 ug/kg of BOL-148 were used intraventricular, to avoid the blood-brain barrier (Bradley and Hance, 1956). BOL-148 is reported to produce no EEG changes in Macaca mulatta, in high dose ranges 110-175 ug/kg (Monroe and Heath, 1961). Saline gave the same response as 1000 ug/kg BOL-148 in cats with permanently implanted EEG electrodes (Eidelberg et al., 1965). In rabbits, 500 ug/kg BOL-148 failed to produce EEG alerting for longer than 15 minutes (Schweigerdt et al., 1966). These studies indicate a lack of effect of BOL-148 on the EEG across a range of species.

BOL-148 has a very slight change in molecular structure compared to LSD, but it has none of the behavioral effects of LSD. LSD causes behavioral arousal in cats whereas BOL-148 produces mild sedation, when the two drugs are administered intraventricularly (Bradley and Hance, 1956). In rabbits, LSD enhances eyeblink conditionining, whereas BOL-148 has a neutral effect (Harvey, 2003). No affective changes in Papio papio are observed after BOL-148 in doses of 2-4 mg/kg (Fairchild et al., 1980).

Table 3 below shows the questionnaire responses for LSD and several LSD derivatives. LSD is the most potent drug, and caused the most positive responses on the questionnaire. BOL-148 is on this table, and there were few positive responses on the questionnaire at doses of 80 ug/kg, or 50 times the active dose LSD. This shows a lack of effect of BOL-148 as reported by human volunteers.

There is some evidence that BOL-148 pre-treatment protects against LSD psychosis. Studies in rabbit have shown that BOL-148 1 mg/kg had no direct temperature effect, as LSD does, but prevented the pyretogenic actions of LSD (Horita and Gogerty, 1958). In humans, BOL-148 did not function as a direct LSD antagonist since intravenous injections of BOL-148 at the height of a LSD trip did not cancel the LSD effects, but pre-treatment with BOL-148 in nonpsychotic humans did produce tolerance to the LSD reaction.

In an experiment with 10 men, pretreatment with BOL-148 for 5 days (1 mg BOL-148 three times daily) significantly attenuated LSD 0.5-1.5 ug/kg psychosis. As shown in Table 3 (below), blood pressure, pupil size and number of positive responses to questionnaire were reduced during LSD challenge 5 days after BOL-148 pretreatment (Isbell et al., 1959). The tolerance-producing effect of BOL-148 does suggest that it may act on similar pathways as LSD.

Some assays have indicated similarities between LSD and BOL-148. For example, LSD and BOL-148 were found to have the same affinity for beta-adrenergic receptors (Dolphin et al., 1978), and were equally effective as MAO and acetylcholinesterase inhibitors in histochemical analysis of rat brain (Shanthaveerappa et al., 1963). However it is important to keep in mind that these samples did not involve the whole organism.

There is one report from 1957 indicating that BOL-148 may function as a hallucinogen in high doses. Two normal volunteers experienced psychic effects when BOL-148 was administered intravenously to total doses of 18 and 22 mg, or equivalent to ~200 LSD doses.
"In man small doses of bromo-LSD are said to produce none of the bizarre psychic effects noted with LSD but this is not the case when bromo-LSD is administered intravenously in large doses. Thus, when constant intravenous infusions of bromo-LSD were given to normal subjects, both experienced psychic changes, which became more severe as the infusion continued and persisted for 3 to 4 hours after the infusion was stopped. No hallucinations were noted but there were feelings initially of drowsiness, depression, anxiety, and apprehension followed by feelings of irritation, restlessness, and tenseness, and later, intensely disagreeable sensations of unreality and depersonalization, inexplicable feelings of strangeness and mild confusion." (Schneckloth,R. 1957)
A relatively large body of work exists on human studies with BOL-148, making it one of the most well characterized LSD analogs. BOL-148 shows that structure-activity relationships can be quite revealing about the mechanism of action of LSD, since substitution at the 2-position can change the activity of the whole molecule. Another important research finding related to BOL-148 research is that LSD does not induce a psychosis by creating a relative deficiency of 5-HT within the brain. BOL-148 has been shown to have more anti-5-HT activity than LSD in vitro and in vivo, thus if LSD worked by blocking 5-HT neurotransmission, BOL-148 would be expected to be a more potent hallucinogenic drug, but BOL-148 is inactive on many accounts.


BRADLEY P. B. and A. J. HANCE (1956). The effects of intraventricular injection of d-lysergic acid diethylamide (LSD 25) and 5-hydroxytryptamine (serotonin) on the electrical activity of the brain of the conscious cat. The Journal of Physiology 132, 50-1P.

Dolphin A., A. Enjalbert, J. P. Tassin, M. Lucas and J. Bockaert (1978). Direct interaction of LSD with central "beta"-adrenergic receptors. Life Sciences 22, 345-352.

Eidelberg E., M. Long and M. K. Miller (1965). Spectrum analysis of EEG changes induced by psychotomimetic agents. International Journal of Neuropharmacology 4, 255-264.

Fairchild M. D., D. J. Jenden, M. R. Mickey and C. Yale (1980). EEG effects of hallucinogens and cannabinoids using sleep-waking behavior as baseline. Pharmacology, Biochemistry, and Behavior 12, 99-105.

Harvey J. A. (2003). Role of the serotonin 5-HT(2A) receptor in learning. Learning & Memory 10, 355-362.

HORITA A. and J. H. GOGERTY (1958). The pyretogenic effect of 5-hydroxytryptophan and its comparison with that of LSD. The Journal of Pharmacology and Experimental Therapeutics 122, 195-200.

ISBELL H., E. J. MINER and C. R. LOGAN (1959). Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25). Psychopharmacologia 1, 20-28.

ISBELL H., E. J. MINER and C. R. LOGAN (1959). Cross tolerance between D-2-brom-lysergic acid diethylamide (BOL-148) and the D-diethylamide of lysergic acid (LSD-25). Psychopharmacologia 1, 109-116.

MONROE R. R. and R. G. HEATH (1961). Effects of lysergic acid and various derivatives on depth and cortical electrograms. Journal of Neuropsychiatry 3, 75-82.

SCHNECKLOTH R., I. H. PAGE, F. DEL GRECO and A. C. CORCORAN (1957). Effects of serotonin antagonists in normal subjects and patients with carcinoid tumors. Circulation 16, 523-532.

Schweigerdt A. K., A. H. Stewart and H. E. Himwich (1966). An electrographic study of d-lysergic acid diethylamide and nine congeners. The Journal of Pharmacology and Experimental Therapeutics 151, 353-359.

SHANTHAVEERAPPA, T. R., K. NANDY and G.H. BOURNE (1963). Histochemical studies on the mechanism of action of the hallucinogens D-lysergic acid diethylamide tartrate (lsd-25) and D-2-bromo-lysergic acid tartrate (bol-148) in rat brain. Acta neuropathologica 3, 29-39.

TURNER W. J. and S. MERLIS (1958). Chemotherapeutic trials in psychosis. III. 2-Brom-d-lysergic acid diethylamide (BOL 148). The American Journal of Psychiatry 114, 751-752.


Anonymous said...

BOL-148 has also been studied as a treatment for cluster headaches:
Beckley Foundation

Anonymous said...

The Beckley Foundation has no additional information about BOL-148 since they fraudulently claim association with that work. Just search for BOL to learn more...