Details obtained by The Scotsman show more than 600 people have been seen by Accident and Emergency (A&E) departments since 2011.
However, the true figure is likely to be significantly higher as only a handful of health boards collate the figures.
Officially known as new psychoactive substances (NPS), concern has been growing for some time about the dangers of the substances, which are readily available on the internet.
While the majority of Scotland’s health boards do not collect figures for the number of A&E admissions due to NPS, a small number recorded statistics which show a worsening picture.
NHS Tayside there were 131 A&E attendances between January and November this year, compared with just 16 for the whole of 2011.
The health board said the figures had grown steadily over the past few years, but urged cautioned over how the information was interpreted.
Shobhan Thakore, a consultant working in A&E, said: “In general, the diagnosis of legal high can only be made if the patient, paramedic or police provide A&E with direct information.
“Patients often present with non-specific symptoms such as dizziness or anxiety and do not disclose what they have taken or in fact that they have taken anything at all.
“Therefore, these figures should be interpreted with caution. It is very difficult to provide an accurate picture.
“The numbers for 2013 onwards are significantly higher than the previous years, but this may be due to a number of factors including drug availability, police awareness and A&E awareness of these substances.”
NHS Greater Glasgow and Clyde recorded 78 instances in the year to November when patients presenting at A&E had mentioned legal highs, that compares with 15 instances in 2014 and 26 in 2013.
NHS Forth Valley said there had been 34 mentions of NPS in admissions to A&E in the year to 17 November. That compares with 47 cases the year before, but up from fewer than five in 2011.
NPS are sold in “head shops” alongside other drug paraphernalia and are often marketed as plant food or bath salts because they cannot be sold for human consumption.
A Scottish Government spokeswoman said: “We acknowledge that there is a need to improve the data and evidence about NPS use and the harm associated with taking these dangerous substances, which is why we are tackling them on a range of fronts.”